The effect of oral clinically used doses of propranolol, atenolol, nifedipine, propranolol + nifedipine, and atenolol + nifedipine on endurance performance and ventilatory responses to graded treadmill testing was studied in 12 healthy physically active men. Maximal exercise duration was reduced by propranolol (8.5%, P less than 0.001) and its combination with nifedipine (11.1%, P less than 0.001), and to a lesser degree by atenolol (3.2%, 0.05 less than P less than 0.1), nifedipine (2.1%, P less than 0.05), and atenolol + nifedipine (3.9%, P less than 0.01). Exercise duration and heart rate (HR) and ventilatory responses to maximal exercise were equivalent with a beta-blocker and its combination with nifedipine. At submaximal exercise, beta-blockade reduced the HR and oxygen uptake, nifedipine accentuated the HR but did not alter ventilation, and all drugs modified the relative oxygen uptake corresponding to 85% of the maximal HR. Physiologic responses to submaximal exercise during combination therapy were similar to those during beta-blockade alone. This study concludes that, in physically active men, nifedipine induces a small impairment of maximal performance, but does not accentuate the reduction in effort tolerance resulting from beta-blockade. Furthermore, HR and ventilatory responses to exercise during combined beta-blockade and calcium antagonism can be predicted from those during beta-blockade alone.