The Bio-Organic Weapon designated U-3 is a warped amalgamation of human, reptile and insect genes. Appearing in Resident Evil 4, this monster was created by scientists under the employ of Osmund Saddler and the Los Illuminados. The fusion of DNA from radically different species resulted in an imperfect, asymmetrical form which was only able to function with the application of a Las Plagas parasite. Its upper body appears humanoid, but its face peels open into a gaping maw and it possesses a long, stretching tentacle in place of a left arm. Its four front and hind legs appeared bonded by a centipede-like fleshy piece of muscle.

Leon S. Kennedy encountered the U-3 (or "It" as Lord Saddler called it) on Saddler's island base and fought against it inside a suspended set of crate rigs. He was able to avoid its attacks and escape the rigs before they all dropped into the chasm below, but the U-3 also escaped and attacked again on the cliff at the other side of the chasm. The monster mutated as it attacked, its back tearing open as its spine erupted from it, sporting a large pair of sharp pincers capable of snapping a man in half. It was also capable of burrowing beneath the ground so that it could take Leon with a surprise attack. After a frantic battle, Leon managed to kill the U-3 by destroying the parasite in its body.