alpha-melanocyte-stimulating hormone (alpha-MSH) is an endogenous neuroimmunomodulatory peptide that inhibits fever and all major forms of experimental inflammation. In humans, concentrations of alpha-MSH are increased at sites of inflammation, and in plasma in inflammatory disorders and after infection of endotoxin. The effects of this 'anti-cytokine' peptide are mediated through alpha-MSH receptors and regulatory circuits in macrophages and neutrophils, and through descending neural anti-inflammatory pathways that originate from alpha-MSH receptors on neurons within the brain.