PURPOSE: This study is to assess the pharmacologic effects of ethanol and its metabolite, acetaldehyde on potassium channels of the corpus cavernosal smooth muscle of the rabbit. MATERIALS AND METHODS: Cavernosal strips from New Zealand white rabbits were harvested and pharmacophysiologic organ bath studies were executed. In equilibrium state after incubation, zaprinast (PDE5 inhibitor) induced relaxations were monitored in strips precontracted with phenylephrine (PE, 10(-4)M). The inhibitory effects of ethanol and acetaldehyde (2, 20, 40, 80 mmol) on zaprinast-induced relaxations were recorded. Pinacidil (K(ATP) channel opener) and phloretin (BK channel opener) were tested to reverse the inhibitory effects of ethanol and acetaldehyde on zaprinast-induced relaxations. RESULTS: Both ethanol and acetaldehyde inhibited the zaprinast-induced relaxations in a dosedependent manner (p<0.05). Both pinacidil and phloretin abolished the inhibition by both ethanol and acetaldehyde (p<0.05). Ethanol and acetaldehyde inhibits cavernosal relaxation, possibly through BK channels and K(ATP) channels. CONCLUSIONS: These results suggest that ethanol and its metabolite may affect the corpus cavernosal smooth muscle directly and lead to consequent erectile dysfunction. Furthermolecular and electrophysiological studies will help reveal the underlying mechanisms to which this process occurs.