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As soon as Chuck Greene and Frank West arrive in the facility, they head for the Shipping Office where they find a security guard at the desk. Chuck approaches him and tells him to stand down and he will not get hurt. The guard gets up and looks over at another guard in the other room, who tosses him a gun as he walks out into the computer room. Chuck and Frank are forced to kill the two guards.
As Chuck and Frank make their way throughout the facility, they encounter dozens of security guards, trying to kill the zombies, though they will open fire upon seeing the pair. Guards also reside in the Security Tower, a fortified tower in the Holding Pens that is filled with armor and weapons. Their base of operations is the Security Outpost, where they monitor the facility. Also in the outpost are lockers available for personnel as well as a lounge area.
Later, while meeting up with Isabela Keyes in the Secure Laboratory, they are interrupted by Marian Mallon, who sends two guards to apprehend the trio. Isabela manages to escape, but returns moments later with a handgun and kills one of the guards, before being knocked out by Harjit Singh. The remaining guard carries Isabela's body to the Director's Office. After Harjit is defeated, Marian initiates self-destruct and escapes with the remaining guard and Isabela.
All remaining guards in the facility are either killed in the blast or evacuated to safety. Should Frank and Chuck fail any case, they will be apprehended and detained by a group of security guards.