Recombinant human tumor necrosis factor alpha (TNF alpha) decreases social exploration and induces weight loss in mice in a dose- and time-dependent manner (2.5-40 micrograms/mouse). To assess the role of interleukin-1 (IL-1) in these effects, mice pretreated with IL-1 receptor antagonist (IL-1ra, 500 micrograms/mouse, i.p.) were injected with 25 micrograms TNF alpha. Pretreatment with IL-1ra antagonized the depressive effects of TNF alpha on behaviour but only partially attenuated the weight loss induced by this cytokine. These results suggest that TNF alpha-induced sickness behaviour is mediated mainly by endogenously released IL-1 whereas metabolic changes are dependent on the release of other additional cytokines.