The cytokine interleukin‐1 (IL‐1), which mediates many responses to infection and injury, induces anorexia and fever through direct actions in the central nervous system. The melanocortin neuropeptides, such as alpha melanocyte‐stimulating hormone (α‐MSH), reportedly antagonize many actions of IL‐1, including fever and anorexia. However, it is unknown whether endogenous melanocortins modulate anorexia induced by IL‐1. The objective of the present study was to establish the effect of endogenous melanocortins on IL‐1‐induced anorexia and fever in the rat. Intracerebroventricular (i.c.v.) injection of IL‐1β caused a significant reduction in food intake and body weight gain, and a rise in core body temperature in conscious rats. Coadministration of the melanocortin‐3/4 receptor (MC3/4‐R) antagonist, SHU9119, reversed IL‐1β‐induced reductions in food intake and body weight, but did not affect the febrile response to IL‐1β. These data suggest IL‐1β may elicit its effects on food intake through the melanocortin system, predominantly via the MC3‐R or MC4‐R. In contrast, IL‐1β‐induced fever does not appear to be mediated or modulated by MC3‐R or MC4‐R activity.