Summary—The mechanism(s) responsible for arterial vasodilation observed following acute administration of racemic carvedilol, a novel vasodilator/beta adrenoceptor antagonist, has been investigated in rats. In conscious spontaneously hypertensive rats, carvedilol (0.03–3.0 mg/kg, iv) produced a dose‐dependent reduction in blood pressure with no significant effect on heart rate. Because cardiac output was relatively unaffected, the antihypertensive response of carvedilol was associated with a dose‐dependent reduction in total peripheral vascular resistance. Submaximal antihypertensive doses of carvedilol were chosen for mechanism of action studies in pithed rats. Carvedilol (0.3 mg/kg, iv) produced a significant inhibition of the β1adrenoceptor mediated positive chronotropic response to isoproterenol. This same dose of carvedilol also inhibited, but to a lesser degree, the β2adrenoceptor mediated vasodepressor response to salbutamol in pithed rats whose blood pressure was elevated by a constant intravenous infusion of angiotensin II. Thus, carvedilol blocks both β1and β2adrenoceptors at antihypertensive doses, with modest selectivity being observed for the β1adrenoceptor subtype. Carvedilol produced significant inhibition of the α1adrenoceptor mediated pressor response to cirazoline in the pithed rat, but had no effect on the α2adrenoceptor mediated pressor response to B‐HT 933, suggesting that carvedilol is also an α1adrenoceptor antagonist at antihypertensive doses. Carvedilol had no effect on the pressor response elicited by angiotensin II, indicating a lack of nonspecific vasodilator activity. The vasopressor response to the calcium channel activator, BAY‐K‐8644, which is mediated through the opening of voltage dependent calcium channels and the subsequent translocation of extracellular calcium, was significantly inhibited by carvedilol (1 mg/kg, iv), suggesting that carvedilol is also a calcium channel antagonist, consistent with our previousin vitrostudies. In anesthetized spontaneously hypertensive rats, the antihypertensive activity of carvedilol was nearly abolished by combined pretreatment of the rats with high doses of the α1adrenoceptor antagonist, prazosin (1 mg/kg, iv), and the nonselective β adrenoceptor antagonist, propranolol (3 mg/kg, iv), suggesting that the majority of the antihypertensive response produced by carvedilol may be accounted for by blockade of β and α1adrenoceptors. We therefore conclude that carvedilol, at antihypertensive doses, is an antagonist of β1, β2, and α1adrenoceptors, and also of calcium channels in vascular smooth muscle. The β1adrenoceptor blocking properties of carvedilol appear to account for the lack of reflex tachycardia that occurs in response to baroreceptor activation, and the arterial vasodilation appears to result largely from selective α1adrenoceptor blockade, with little or no contribution being derived