Past research shows that violent video game exposure increases aggressive thoughts, angry feelings, physiological arousal, aggressive behaviors, and decreases helpful behaviors. However, no research has experimentally examined violent video game effects on physiological desensitization, defined as showing less physiological arousal to violence in the real world after exposure to video game violence in the virtual world. This experiment attempts to fill this gap. Participants reported their media habits and then played one of eight violent or nonviolent video games for 20 min. Next, participants watched a 10-min videotape containing scenes of real-life violence while heart rate (HR) and galvanic skin response (GSR) were monitored. Participants who previously played a violent video game had lower HR and GSR while viewing filmed real violence, demonstrating a physiological desensitization to violence. Results are interpreted using an expanded version of the General Aggression Model. Links between desensitization, antisocial, and prosocial behavior are discussed.