The mode of the ATP-induced vasoconstriction in the internal carotid artery was studied from the physiological and pharmacological points of view. ATP caused dose-dependent vasoconstrictions in the canine internal carotid artery. The ATP-induced vasoconstriction was not affected by pretreatment with phenoxybenzamine, propranolol, atropine, cyproheptadine, or tetrodotoxin. Verapamil suppressed the contractile response. ATP produced no vasoconstriction in a calcium-free Krebs solution containing 1 m M EGTA nor augmentation of Ca<sup>2+</sup>-induced contraction in potassium-depolarized tissues. These results suggest that an increase of potential-dependent Ca<sup>2+</sup> influx into the arterial smooth muscle may play a major role in the ATP-induced vasoconstriction.