Beta-adrenergic blocking agents are commonly used in combination with digitalis to control excessive heart rate during exercise in patients with chronic atrial fibrillation. However, little is known about the effect of betaadrenergic blockade on exercise capacity in these patients. Accordingly, a randomized, double-blind, crossover placebo-controlled study was performed to assess the efficacy of Celiprolol, a new cardioselective betablocker with partial intrinsic sympathomimetic activity, on exercise performance in nine men with chronic atrial fibrillation. All but one patient was receiving maintenance digitalis during the study. Heart rate, blood pressure and gas exchange variables were measured at rest and during treadmill exercise testing while the patients were receiving maintenance Celiprolol or placebo. Significant reductions in heart rate and systolic blood pressure compared with control values were observed at submaximal exercise, at the gas exchange anaerobic threshold and at maximal exertion while the patients were taking Celiprolol. However, oxygen uptake at the gas exchange anaerobic threshold during Celiprolol therapy was 12.3 versus 14.0 ml oxygen/kg per min during placebo administration (a 12% difference, p < 0.01). Similarly, oxygen uptake at maximal exertion during Celiprolol therapy was 17.6 versus 21.0 ml/kg per min during placebo administration (a 16% difference, p < 0.01). Treadmill time was also reduced during the Celiprolol phase compared with placebo (11.3 versus 10.3 minutes; a 19% difference, p < 0.01). These results indicate that in patients with atrial fibrillation the major beneficial effects of beta—adrenergic blockade-reduced submaximal and maximal exercise heart rate and blood pressure—must be weighed against the decrease in exercise capacity.