1. We measured the effect of intravenous and intracerebroventricular injections of alpha-melanocyte stimulating hormone (alpha-MSH) on changes in body temperature and serum iron concentration following i.v. injection of endotoxin in rabbits. 2. Intravenous alpha-MSH (2.5 micrograms) significantly reduced both phases of endotoxin fever and attenuated the fall in serum iron concentration which follows endotoxin injection. 3. Intracerebroventricular alpha-MSH (200 ng) reduced only the second phase of the fever and had no effect on the fall in the serum iron concentrations. 4. We conclude that alpha-MSH, in doses that are known to inhibit endogenous pyrogen fever, inhibits the fever induced by endotoxin in rabbits, probably by blocking the actions of endogenous pyrogens mediating the endotoxin fever.