To study the role of central IL-1 receptors in the effects of recombinant human IL-1 beta (IL-1 beta) on behavior and body weight, intracerebroventricular (i.c.v.) injection of the specific antagonist of IL-1 receptors, IL-1ra, was administered to mice injected intraperitoneally (i.p.) and i.c.v. with various doses of IL-1 beta. Doses of 500 ng i.p. IL-1 beta and 900 pg i.c.v. IL-1 beta induced a comparable decrease in social behavior and loss of body weight. Pretreatment with IL-1ra (1.8 micrograms/mouse, i.c.v.) blocked the effects of i.c.v. IL-1 beta (900 pg/mouse) on social behavior. i.c.v. IL-1ra (3.6 micrograms/mouse) also attenuated the effects of i.p. IL-1 beta (500 ng/mouse) on social behavior and change in body weight, suggesting that the effects of peripheral IL-1 beta are centrally mediated.