Interferon, which is produced during viral infections, has cognitive and neurological effects in humans. A dose of 1600 U/g of mouse interferon-alpha significantly depressed horizontal activity, head pokes into a food chamber, and food intake in mice 10 hr and 24 hr after injection. An 800 U/g dose had only slight effects on horizontal activity and food intake, whereas a 400 U/g dose had no effect. There was no evidence of sensitization to interferon when a second 400 U/g dose was given after the 1600 U/g dose. The results imply that mouse interferon-alpha can be used in mice as a model for studying the fatigue and anorexia produced by interferon.