It is an asymmetric game in the following respects: One player controls the Space Marine Terminators, and the other player controls the Tyranid Genestealers. The game is set on a modular board made up of various board sections which represent corridors and rooms and which can be freely arranged and locked together like a jigsaw puzzle to represent the interior of a space hulk. Besides a space hulk, similar skirmishes between Space Marine Terminators and Genestealers can also be set in other environments. Space Marine Terminators were originally only used in Space Hulk-type scenarios, but rules were added in White Dwarf and subsequent releases of Warhammer 40,000 and Epic for their deployment in conventional battles in limited numbers as elite troops. Space Marine Terminators are described in game lore as veterans who have earned the right to don special armour. Since the 1990s, subsequent games have absorbed them as part of the overall Tyranid army, where they serve as the shock troops. Genestealers were described in the first edition of Warhammer 40,000, but they were very different from their Space Hulk incarnation, which was more influenced by the xenomorphs depicted in the Alien franchise. Space hulks may house many threats: genestealers human followers of the dark gods of Chaos daemons and Orks, who use space hulks as their standard method of interstellar travel. Space hulks are often agglomerations of multiple ships, fused together by the magical influence of the Warp, a kind of hyperspace. In Warhammer 40,000, a 'space hulk' is any massive derelict space ship.

The other player takes the role of Tyranid Genestealers, an aggressive alien species which have made their home aboard such masses. One player takes the role of Space Marine Terminators, superhuman elite soldiers who have been sent to investigate such a space hulk. In the game, a 'space hulk' is a mass of ancient, derelict space ships, asteroids, and other assorted space debris. The game is set in the fictional universe of Warhammer 40,000. Space Hulk is a board game for two players by Games Workshop.

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