We tested the hypothesis that celiprolol, a beta-1 adrenoceptor antagonist with the ancillary property of beta-2-mediated vasodilation, would increase blood flow to active muscles during exercise and result in less impairment of exercise performance compared with the beta-1 antagonist atenolol. After an initial 3-wk washout phase, 11 untrained hypertensive men participated in a 6-wk crossover study of the two drugs. Each treatment phase was followed by a 3-wk placebo phase. Resting forearm and calf vascular resistance measured by venous occlusion plethysmography and submaximal and maximal bicycle ergometry exercise responses were evaluated at the end of each treatment and placebo phase. Celiprolol significantly decreased resting forearm and calf vascular resistance whereas atenolol had no significant effect. Neither beta-blocker significantly affected submaximal exercise oxygen uptake, rate of perceived exertion, minute ventilation, or respiratory exchange ratio. Both beta-blockers significantly and similarly decreased peak oxygen uptake; celiprolol 23.9 +/- 1.7, atenolol 24.9 +/- 1.7, placebo 27.3 +/- 1.3 ml.kg-1.min-1. Our findings suggest that during exercise while on beta-blockade, other factors such as sympathetic vasoconstriction or local metabolic vasodilation may override beta-2-mediated vasodilation. Thus, the addition of beta-2 agonism to beta-1 antagonism decreases resting vascular resistance but offers no advantage over conventional beta-1 blockade therapy during exercise.