Anorexia is a common response to infection which is thought to be mediated, at least in part, by interleukin (IL-1), an immunoregulatory peptide secreted by activated monocytes. Cholecystokinin (CCK) is a neuropeptide that suppresses food intake and gastric emptying when injected into healthy animals. There is increasing evidence of bidirectional interactions between neuropeptides, immune cell function, and secretion of immunoregulatory cytokines. Therefore, the present study was undertaken to determine if administration of L364,718 (L364), a CCK receptor antagonist, might block the anorexigenic effects of recombinant human IL-1 alpha (IL-1 alpha) in rats. We report that injection of IL-1 alpha significantly increased plasma CCK 1 h after injection, and decreased food intake and emptying of gastric contents. Pretreatment with 1 mg/kg L364 partially blocked the decrease in food intake and gastric stasis induced by IL-1 alpha. We conclude CCK may mediate, at least in part, IL-1 alpha-induced anorexia.