Inflammation is generally conceptualized in terms of cells, mediators, and events in the periphery, with no consideration of an influence of the central nervous system (CNS). However, the neuroendocrine peptide alpha-melanocyte stimulating hormone (alpha-MSH) is anti-inflammatory when given systemically and this molecule reaches the brain to exert another effect: fever reduction. Tests on mice indicate that alpha-MSH can act solely within the CNS to inhibit inflammation in the skin. This observation indicates that the central nervous system can inhibit peripheral inflammation via action of alpha-MSH molecules and it further strengthens the idea of neural/endocrine modulation of the host responses.