Recent research indicates that the proopiomelanocortin derivative Α-melano-cyte stimulating hormone (Α-MSH) is a significant modulator of host reactions including fever and inflammation. Although the precise mechanism of action is still unknown, cytokine antagonism is believed to be responsible for at least a part of its anti-inflammatory/antipyretic influence:Α-MSH antagonizes pyrogenic and proinflammatory effects of cytokines such as interleukin-1(IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), and interferonΓ(IFNΓ).Although it is clear that the peptide can act within the brain to inhibit fever and peripheral inflammation, an anti-inflammatory effect on a peripheral target was evidenced in animals with transection of the spinal cord. Recent data show thatΑ-MSH is significant also in human disorders such as AIDS, rheumatoid arthritis, and myocardial infarction. This molecule is believed to be a key factor in neuroirnmunomodulation and it may be useful as a therapeutic agent in control of inflammatory reactions.