The antihypertensive effects of nitrendipine were evaluated in 12 subjects with hypertension, one of whom could not tolerate the drug for more than 3 days; hence hemodynamics were studied in the 11 subjects who were treated for 2 wk. In one patient taking 40 mg twice a day, blood pressure reduction was associated with a hemodynamic pattern of hyperkinetic circulation. Of the other 10 subjects, all of whom were taking 20 mg twice a day, two did not respond, but 8 had significant reduction in mean arterial pressure (136 +/- 4.3 to 106 +/- 3.2 mm Hg) resulting from a decrease in total peripheral resistance (52 +/- 3.7 to 35 +/- 2.6 U X m2). Changes in cardiac output, heart rate, and cardiopulmonary volume varied widely among subjects, such that average changes did not attain significance. Heart rate and cardiopulmonary volume, however, changed in the same direction, which suggests that the alterations in both were related to the degree of reflex sympathetic stimulation induced by nitrendipine. Plasma renin activity (PRA) increased during treatment (2.6 +/- 1.0 to 9.3 +/- 4.1 ng/ml/hr), whereas the increase in plasma aldosterone (PA) levels did not attain significance (13.7 +/- 1.6 to 21.5 +/- 4.5 ng/dl). As a result, PA/PRA decreased (16.1 +/- 4.9 to 9.4 +/- 2.6). These results suggest that calcium entry blockade might have interfered with steroidogenesis, thus blunting the effect of increased PRA. Finally, blood pressure response to nitrendipine in the whole group correlated inversely with pretreatment PRA (r = -0.88), suggesting greater activity of the drug in low-renin hypertension.