Ten male patients with essential hypertension were studied on a constant diet (100 mEq of sodium daily) while on placebo, immediately following a 20-mg oral dose of nitrendipine, and during 1 week of nitrendipine therapy (10 mg twice daily). After 2 weeks of outpatient follow-up on 20-40 mg nitrendipine daily, the patients were readmitted and restudied with the same protocol. Glomerular filtration rate, effective renal blood flow, blood volume, and cardiac output were determined isotopically. Free water clearance and osmolar clearance following a water load were also measured. Twenty-four-hour urinary creatinine and electrolyte excretion were measured during the hospitalization periods. Blood pressure decreased significantly during the acute and chronic periods when compared to placebo. During the first 7 days of nitrendipine treatment, urinary sodium excretion increased significantly from control, and a mean deficit of 148 +/- 7 mEq (p less than 0.001) was calculated. There was a mean weight loss of 1.0 +/- 0.1 kg (p less than 0.05) after a week of treatment. Glomerular filtration rate, renal blood flow, blood volume, cardiac output, plasma renin activity, plasma catecholamines, and urinary aldosterone remained unchanged from control in both the acute and chronic periods. Compared to the placebo period, free water clearance (1.8 +/- 0.6 versus 2.9 +/- 0.5 ml/min; p less than 0.05) and osmolar clearance (1.9 +/- 0.3 versus 2.9 +/- 0.5 ml/min; p less than 0.05) increased significantly in the chronic period. The natriuresis and diuresis associated with nitrendipine therapy without any changes in renal function may represent a direct renal tubular effect of the drug.