The present study was undertaken to investigate the effects of intracavernosal injections of adrenomedullin, a novel hypotensive peptide, on penile erection in anesthetized cats. Responses to adrenomedullin were compared to those elicited by intracavernosal injection of the control triple-drug combination (1.65 mg papaverine, 25 micrograms phentolamine, and 0.5 microgram prostaglandin E1). Intracavernosal injections of adrenomedullin in doses of 0.1-1.0 nmol elicited dose-related increases in cavernosal pressure and penile length. The maximal effect of adrenomedullin injection on cavernosal pressure was an 8-fold increase in pressure, which was 74% of that induced by the triple-drug combination. The maximal effect on penile length was a 43% increase when compared to baseline value, which was comparable to that induced by the triple-drug combination. The duration of the peak pressure and total duration of the peptide effect were significantly shorter in response to the 1 nmol dose of adrenomedullin than was observed with the control triple-drug combination. Intracavernous injection of the control triple-drug combination resulted in a significantly greater decrease in systemic arterial blood pressure than did adrenomedullin. Erectile responses to adrenomedullin were not altered following administration of the nitric oxide synthase inhibitor. N omega-nitro-L-arginine, at a time when erectile responses to acetylcholine were significantly reduced. These data demonstrate that intracavernous injection of adrenomedullin induces a short-lived erection in cats that is not due to the release of nitric oxide.