A cDNA that codes for the polypeptide hormone precursor proopiomelanocortin (POMC) was cloned and sequenced from a gar (Lepisosteus osseus) pituitary cDNA library. The gar POMC cDNA is 1237 bp and contains a 780-bp open reading frame. The deduced amino acid sequence for gar POMC is 259 amino acids in length. The general organization of gar POMC is very similar to that of other gnathostome POMC sequences. The beta-endorphin sequence had 91% sequence identity with sockeye A beta-endorphin and 71% sequence identity with Xenopus laevis beta-endorphin. Three melanocyte-stimulating hormone (MSH) core sequences [HFR(W)] were detected. The gar alpha-MSH sequence was identical to the alpha-MSH sequence in rat POMC. The gar beta-MSH sequence had 77% sequence identity with salmonid forms of beta-MSH and 53% sequence identity with tetrapod forms of beta-MSH. The gamma-MSH region of gar POMC only had 26% primary sequence identity with tetrapod gamma-MSH sequences. Gar gamma-MSH had an incomplete MSH core sequence (HRF), an apparent internal deletion of five amino acids, and lacked flanking paired basic amino acids essential for proteolytic cleavage. The apparent degenerate nature of gar gamma-MSH is discussed in light of the absence of this sequence in salmonid fish.