A proopiomelanocortin (POMC)-like hormone has been cloned and sequenced from a pituitary cDNA library of upstream migrant (prespawning) sea lamprey, Petromyzon marinus. The clone, designated LPP-1, consisted of 986 nucleotides, with an open reading frame of 277 amino acids, including a signal peptide of 22 amino acids. Like POMCs from more recently evolved vertebrates, lamprey POMC contained domains which corresponded to alpha-MSH, ACTH, and beta-endorphin. However, sequences corresponding to gamma- and beta-MSH are absent or likely nonfunctional, respectively, in this cDNA. Northern blot analyses showed low but detectable expression levels of LPP-1 in larvae and strong expression in parasitic adults and prespawning animals. These observations indicate that a recognizable POMC, distinct from proenkephalin, has an ancient lineage within subphylum Vertebrata, likely dating back to the last common ancestor of the lamprey and gnathostome lines. (C) 1995 Academic Press, Inc.