The effects of infection of mice with influenza virus on ingestive behavior were assessed by both 22-h intake of food pellets, and intake of sweetened milk in a 30-minute access period. Infection with a lethal dose of virus resulted in losses in body weight as well as a reduction in food pellet intake. By contrast, infection with a sublethal dose of virus decreased body weight and food pellet intake to a lesser extent, but did not alter milk intake. Acute intraperitoneal injection of endotoxin (LPS, 0.3-5 micrograms), interleukin-1 alpha (IL-1 alpha, 50-100 ng) or IL-1 beta (100 ng) reduced milk intake, suggesting that the reduction of ingestive behavior may be associated with immune activation in general, and IL-1 in particular Pretreatment of the mice with the cyclooxygenase inhibitor, indomethacin (10 mg/kg SC) substantially attenuated, but did not completely reverse, the reduction in milk intake by LPS and IL-1. However, chronic treatment with indomethacin failed to alter the body weight or the intake of sweetened milk in influenza-infected mice, although there was some attenuation of the reduction in food intake. These results suggest that although IL-1 may play a role in the anorexia caused by influenza virus infection, it is not the only factor involved.