Nipradilol competitively antagonized norepinephrine- or phenylephrine-induced contractile responses of guinea-pig thoracic aorta. These actions of nipradilol were about 6 times less potent than those of phentolamine. Nitroglycerin showed a non-competitive antagonistic action on norepinephrine-induced contractions of aorta. Furthermore, nipradilol competitively inhibited norepinephrine-induced contractions of rat vas deferens and dose-dependently reduced the phenylephrine-induced inhibitory responses in rabbit ileum. These antagonistic actions of nipradilol were 30 to 100 times less potent than those of phentolamine. Nitroglycerin did not appreciably affect these alpha-adrenoceptor mediated responses in rat vas deferens and rabbit ileum. The inhibitory action of clonidine on the twitch contraction of rat vas deferens produced by intramural stimulation was only slightly antagonized by nipradilol (pA2 = 5.4). Nipradilol and nitroglycerin showed a non-competitive antagonistic action on clonidine-induced contractions of canine saphenous vein after the exposure to phenoxybenzamine, while phentolamine competitively inhibited the clonidine responses. These results suggest that nipradilol possesses an alpha 1-adrenoceptor blocking action; it possesses very weak or practically no presynaptic alpha 2-blocking activity but shows a non-competitive antagonistic action on postsynaptic alpha 2-adrenoceptor mediated contractile responses.