1. The influence of catechol-O-methyltransferase inhibitor U-0521 on isotonic contraction of isolated rat vas deferens was examined to determine optimal concentration and nonspecific effects. 2. Maximum responses to (-)-epinephrine were increased at 0.4 μM and 1 μM concentrations of U-0521. Epinephrine responses were progressively decreased in the presence of higher concentrations (10 μM, 30 μM and 100 μM) Of U-0521. 3. The response to the nonadrenergic agonist neurokinin A was similarly depressed in the presence of 100 μM U-0521. 4. U-0521 not only inhibits COMT, at concentrations above 1 μM it nonspecifically depresses contraction of the rat vas deferens by both adrenergic and nonadrenergic agonists.