Background—Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that &agr;-adrenergic–blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol.Methods and Results—Forearm vascular resistance responses to isometric handgrip and cold pressor test were determined by plethysmography before and during adrenergic receptor blockade in prospective randomized trials. Acute effects were assessed in a crossover trial in normal subjects (single dose of 25 mg carvedilol, 100 mg metoprolol tartrate, and placebo). Chronic effects (25 mg carvedilol BID versus 200 mg extended-release metoprolol succinate daily for 6 months) were assessed in a parallel group trial of chronic heart failure subjects. In normal subjects, carvedilol decreased forearm vascular resistance responses to adrenergic stimuli when compared with metoprolol and placebo (isometric handgrip −3.5 U for carvedilol versus −1.2 U for metoprolol and −2.2 U for placebo,P=0.15; cold pressor test 3.1±8.9 U for carvedilol versus 9.0±2.7 U for metoprolol and 8.2±5.8 U for placebo,P<0.05). In heart failure subjects, vasomotor responses to isometric handgrip and cold pressor test did not differ between treatment groups.Conclusions—Acute administration of carvedilol attenuates the vasoconstriction response to adrenergic stimuli when compared with placebo and metoprolol in normal subjects, whereas chronic administration of carvedilol does not attenuate the vasoconstrictor response to adrenergic stimuli when compared with metoprolol in heart failure subjects. These data suggest that long-term benefits of carvedilol in heart failure are not mediated by &agr;-adrenergic blockade.