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Set in the near future the exploits of gun sharks (hitmen) Finnigan "Finny" Sinister and Ramone "Ray" Dexter in the city of Downlode, sprawled across Central Europe "like a hit and run victim". Occasional stories have taken place in other cities, or off planet. The size of Downlode is never specified in the strip, but it appears to stretch from Spain to eastern Europe. The appearance of the city largely depends on the artist of the particular storyline, often it appears to be styled after the former soviet bloc, with many statues and wide boulevards, plus dilapidated cars such as Trabants and VW Beetles. However in other strips the city looks clean and futuristic, like Mega City One. The story "London Town" shows that London and Great Britain still exist separate from Downlode.
In early strips the police used hover-cars with "Polizei" written on the side, however more recently they have been seen driving generic saloon cars resembling Ford Crown Victorias. These are painted in a similar way to the cars of the LAPD and have DCPD written on them. Sinister and Dexter themselves drive a 1950s Edsel, this started out as a hardtop but in the story "Alibi Of Broadway" had its roof torn off and was re-built as a convertible. This car is frequently crashed into things or shot at but somehow is always repaired perfectly in time for the next story. Hover Car technology seems to exist too, and in some stories appears to have been retrofitted to old cars such as Checker Cabs. Advanced robots are occasionally seen in the stories, but appear to be very rare, and are usually controlled by humans and are unable to think for themselves. Some characters also have several cyborg implants, including Ramone himself who has a "Fony Headcase" television implanted into his eyes. In one story a malfunction in this temporarily gave him the ability to see in infra-red and detect a small hole in a crime-bosses' personal forcefield (referred to as a very rare and expensive technology).
The atmosphere of the stories suggests a time of economic recession, with many references made to sophisticated army hardware being sold off to the highest bidder, usually criminal gangs. Additionally many strips feature the city looking worn and run-down even in "rich" areas. In the story "Mother 'Lode And The Red Admiral" it is mentioned that Korea has developed cold fusion and become the world's richest nation.
Ramone uses a pair of "Ruger Nines", often drawn a silver 9mm pistols, or occasionally as revolvers. Sinister uses a "Minigun" which is nothing like the real-world minigun. In most stories it resembles a small pump-action shotgun and can fire different kinds of bullets, including high explosives. In other stories (with different artists) the gun looks like a large double-barrelled revolver or a small machine pistol.

In early stories the duo work as freelance hit-men, taking contracts from their "fact-totem", a PDA-like device, and killing people for money. The kingpin of crime in these early stories is Holy Moses Tanenbaum.
Eventually a large price is put on the head of Holy Moses himself, expecting Sinister and Dexter to take the contract he sends hit-men to kill them, after killing these they decide to take the contract, as their reputation would dictate they have to take the toughest jobs. After a battle which results in the duo both being nearly killed Holy Moses is killed and the person who put out the contract is revealed to be his wife, Demi Octavo.
A brief period of gang violence follows as various gangs attempt to take control of the city's underworld for themselves. Eventually The Czar, moblord of the Russian mafia calls a conference of gang leaders in an attempt to resolve the situation and hires Sinister and Dexter as security for the meeting. During the meeting, Sinister and Dexter discover that, naturally, every single gang has made plans to assassinate the other gang leaders. After these are fought off The Czar reveals "himself" to be a robot double outfitted with a close-focus nuke in its chest cavity. With the gang leaders dead The Czar is able to take over the underworld for himself.
Following the gang-war, Sinister and Dexter are hired by an accountant working for a Mr Bronsky "Ballpeen" Hammer as protection to 'expedite' the handover of the year-end accounts. The rendezvous between the accountant and Mr Hammer's men in Fred Quimby Municipal Park is violently interrupted by the Department of Taxation, causing the "Infamous Audit Showdown of '66". As a result of the carnage, Sinister and Dexter decide to take a holiday and The Czar recommends that they visit a nightclub in Asbestopol known as the Bawdwalk. At the club a pair of hired muscle known as Buddy Boom and Buddy Bing are threatening the club owner, Kilopatra, so Sinister and Dexter step in to help him and scare off the heavies, thus picking themselves up a holiday job.
Kilopatra sends the pair off to pay a visit to local mob-king Philly O'Fisch, as it was he who sent the two heavies after Kilopatra. Sinister and Dexter kill the two Buddies and warn Philly off Kilopatra under threat of taking one of the many contracts that Philly has on his head. When they return from this job, the run into Demi Octavo who is at the nightclub under a pseudonym, she tells the pair that the word spread that she was the one who put out the hit on Holy Moses Tanembaum so she decided to escape Downlode. The Czar suggested that she head to the Bawdwalk, which convinces Sinister and Dexter that The Czar has set them all up.
The pair invade Philly's island lair and kill him and all of his minions and return to Downlode to take out the Czar using a giant, cyborg alligator that ticks. After this, Demi Octavo takes over as mob-queen and hires Sinister and Dexter as her personal guardians.
Stories from now on generally revolve around them protecting her empire, though occasionally they also take contracts from other people. During this time Demi's kid sister, Billi Octavo, decides to become a Gunshark, but a misunderstanding results in her killing some respected city dignitaries. During the ensuing police chase Sinister explains the unwritten "Gunshark Code" that they never kill cops or "innocents". Later Billi hacks into the police database and finds the dignitaries she killed where actually guilty of "perverted" crimes and it had been covered up. She released this data to the media and the police where forced to abandon the hunt. It is also revealed most rank-and-file police officers actually support Gunsharks, because they only kill other criminals which results in less criminals overall.
Later Dexter begins to see visions on his "Headcase" TV which suggest he is a wanted serial killer, the Blemvoi Butcher. It turns out the actual killer also has a "Headcase" and the signals have got confused. The Butcher lures the pair and two police officers, including the "by-the-book" Tracey Weld, into a trap. Dexter kills the butcher and this eventually leads to his becoming romantically involved with Weld.
Later Demi Octavo is killed and the city once again descends into turmoil. During this time the pair "train" another Gunshark, Kal Kutter.
Another mob boss, called Apellido, begins to take over the city and sends a huge squad of "bullet monkeys" (inferior but cheaper gunsharks) after Billi Octavo. Sinister attempts to get her out of the city but the other hitmen are chasing the two. Meanwhile Dexter is with Detective Weld when he hears the news and rushes out of the house with his guns drawn. By chance he is seen by a police officer who tells him to freeze, before going to get out his handcuffs. Dexter misinterprets this as the officer going for his gun and kills him, thereby breaking the gunshark code. He escapes but doesn't get very far before being surrounded. Fearful of being tortured in prison a standoff ensues, and he is eventually shot by Weld. Sinister is last seen speeding out of the city, with a wounded Billi octavo in the car, still pursued by the bullet monkeys.
The story line at the end (over the instalments "...and Death shall have no dumb minions" and "Festive Spirits") seemed to suggest that the deadly duo where both dead. However, this didn't stop some one-page "gag strips" from appearing.
This issue has now been addressed in passing as part of the twist in the, initially apparently unconnected, series Malone. The "Festive Spirits" story, in which both appeared as skeletal zombies who where apparently ignored by their old friends, is hinted at merely being one of Malone's dreams.
After surviving the showdown with his boss, Apellido, Sinister changed his face and took drugs to try to forget his past, fleeing offworld to Generica. It wasn't until Rocky Rhodes told him of his true identity that he returned to Downlode City to get revenge on Apellido making sure he knows that he's now alive. It was also revealed that Ramone also survived the shooting but was rendered quadriplegic.
Sinister allowed himself to be captured and was sent to the same prison as Ramone, with a plan to escape. After enlisting the help of two other prisoners, he executes the breakout and escapes with Ramone in a wheelchair. Heading to an old doctor friend it is revealed Ramone has been kept immobilised by an implant in his spine. With this removed, and surviving an attack by another Apellido hit-squad, the head for a run-down lockup. There Sinister stashed the Edsel and their old guns. They collect these and drive back into Downlode to again work as gunsharks, bringing the series full circle.

Finnigan Rapunzel Sinister, is Irish hitman and known to be superstitious. He is also married.
Ramone Algonquin Winnibago Dexter is Spanish and is known to be a "fashion guru" and womanizer.
Associates include:
Satan Brink (Deceased), fellow gunshark and street fighter from Tasmania
Anopheles Bunkum (Deceased), former police detective
Floppy Dick (Deceased), a friend of the hitmen
Billy Fix, a Tourettes sufferer in Download Penitentiary
Wendy Go, Rocky Rhodes' wife and barmaid at the Bar None
Carrie Hosanna, Finnigan's wife and fellow gunshark
"Nervous" Rex Monday (Deceased), snitch and friend to the hitmen
Billi Octavo, younger sister of Demi and friend to the hitmen
Demi Octavo (Deceased), girlfriend of "Holy" Moses Tannebaum and former crime boss
Rocky Rhodes, a former cop and friend, owner of the Bar None
Lizzy Solemnis, a singer on the planet Generica
The Surgeon, a surgeon for the criminal underworld
Clayton Tushman, Sinister & Dexter's Lawyer
Tonto Vega (Deceased), a Sioux Indian and wannabe gunshark
Tracy Weld, a rookie cop and Ramone's girlfriend
Deakus Whisk, a bank robber in Download Penitentiary
SteamPunk Willy, a former gunshark whose brain was encased in a total body prosthesis.
Kal Cutter, former student of Sinister & Dexter
Major villains include:
The Apellido Mob:
Apellido, current Crime Lord of Download City
Ronko, Apellido's chief enforcer. Described as being "like the bog roll: Rough, abrasive and hard on everyone's ass". Killed by Dexter.
Lars Maybach, Apellido's chief banker
Charlie Bigelow, one of Apellido's enforcer
Chevy Brakes, a minor enforcer
The Mover's Mob:
"Holy" Moses Tannebaum (The Mover), first Crime Lord of Download City. Was killed by the duo on the orders of Demi Octavo. Recently, an another "Holy" Moses revealed himself to be "The Mover"
Miss Deeds, The Mover's assistant
John Croak, his Second-in-command
Cane Broadus, Kal Cutter's partner in crime
Telemachus Gore (Deceased), corrupt cop and former Crime Lord/Marshal
Serge, a gangster on the planet Generica