Concentrations of vasoactive intestinal polypeptide were measured in blood drawn from the cavernous spaces of corpus cavernosum of the human penis during tumescence and erection, and the effect of injecting the polypeptide into the cavernous spaces was studied. A significant release of the polypeptide was shown during tumescence and erection. Injection of exogenous vasoactive intestinal polypeptide induced erection. These findings support the concept of vasoactive intestinal polypeptide as a neurotransmitter in penile erection and suggest that it might have a clinical use in patients suffering from erectile dysfunction.