Interleukin-1 beta (IL-1), a cytokine released from inflammatory cells, is thought to be involved in the anorexia associated with severe infection. To assess a possible role of the amino acid sequence found in the supposed IL-1 receptor binding sites, we determined the antagonistic effects of alpha-melanocyte-stimulating hormone (MSH) and the carboxyl-terminal tripeptide of alpha-MSH-(11-13) (alpha-MSH-(11-13)) on the anorexia induced by intracerebroventricular (i.c.v.) administration of 0.5 pmol IL-1. The parent alpha-MSH molecule completely prevented the induction of anorexia by IL-1 at both doses tested, 0.5 and 5.0 pmol. In contrast, alpha-MSH-(11-13) prevented the IL-1-induced anorexia only at 5.0 pmol, but not at 0.5 pmol. Intracerebroventricular injection of 5 pmol of the parent alpha-MSH molecule alone temporarily decreased food consumption at 1-2 h; 5.0 pmol of alpha-MSH-(11-13) alone did not affect food consumption. These data indicate that alpha-MSH can antagonize the anorexic effects of IL-1. The carboxyl-terminal tripeptide portion of alpha-MSH may be important for the antagonistic action of alpha-MSH on the anorexia induced by IL-1.