To investigate the role of interleukin-1 (IL-1) in the decrease in food-motivated behavior after peripheral administration of lipopolysaccharide (LPS), rats trained to press a lever for food on a fixed ratio 10 schedule were pre-treated with a recombinant human IL-1 receptor antagonist (IL-1ra). This endogenous cytokine has been shown to block most of the inflammatory and immune effects of IL-1 both in vitro and in vivo. Intraperitoneal (i.p.) injection of LPS (400 micrograms/kg) decreased operant responding for food to 30-60% of baseline for 1-4 h. Response rates gradually recovered, but were still below control levels 8 and 24 h post-injection. Neither i.p. (8 mg/kg) nor intracerebroventricular (288 micrograms/kg) administration of IL-1ra blocked the effects of peripherally administered LPS on food-motivated behavior. These results suggest that the effects of LPS on this behavior are not mediated by the release of IL-1.