Beta-blocker therapy remains controversial in patients with mitral stenosis. In this randomized, double-blind, crossover, placebo-controlled study, the effects of atenolol (50 and 100 mg/day) were assessed in 15 patients (aged 46 +/- 11 years) with mitral stenosis (mean valve area 1.0 +/- 0.4 cm2; New York Heart Association class II or III) at rest and during upright bicycle ergometry. Doppler echocardiography was used to compare heart rate, cardiac and stroke volume indexes, diastolic filling period, and peak and mean transmitral gradients; a metabolic cart was used to obtain maximal oxygen consumption, carbon dioxide production, and anaerobic threshold. Beta-blocking therapy did not improve exercise time, external work, maximal oxygen consumption rate, or anaerobic threshold. Compared with placebo, maximal oxygen consumption rate and cardiac index decreased (p < 0.05) > 11% and > 20%, respectively, with atenolol at peak exercise. Although heart rate was reduced > 20% and diastolic filling period prolonged > 40% by atenolol at rest and exercise (p < 0.05), stroke volume index changed little compared with placebo. The data suggest that despite lower transvalvular pressure gradients, little benefit in exercise performance is achieved with beta-blocker therapy in patients with severe mitral stenosis.