The effect of helodermin, a member of the secretin/vasoactive intestinal polypeptide (VIP)/peptide histidine isoleucine (PHI) family of peptides, on pituitary prolactin (PRL) secretion was examined in the rat. Either i.c.v. or i.v. injection of helodermin resulted in a dose-related increase in plasma PRL levels in urethane-anesthetized male rats. At the doses tested the potency of helodermin to raise plasma PRL levels was greater than that of rat PHI and porcine PHI, and as great as that of VIP.