Although adrenal stimulatory effects of ACTH and pigmentary influences of MSH have been known for decades, it has become clear only recently that melanocortin peptides have multiple effects upon the host. These effects range from modulation of fever and inflammation to control of food intake, autonomic functions, and exocrine secretions. Recognition and cloning of melanocortin receptors (MCRs) has greatly improved understanding of peptide-target cell interactions. Synthetic melanocortins, with selective affinities for specific MCRs, could be the basis for new classes of therapeutic molecules. This review examines promising targets for a-MSH and closely related peptides in inflammatory disorders.