Nitrendipine, a 1,4-dihydropyridine derivative, is a new calcium entry blocker with marked antihypertensive effects. Because relatively few data are available regarding its renal effects, we studied the drug's action on renal hemodynamics and electrolyte excretion in normal male volunteers. During sustained water diuresis, 5 to 10 mg nitrendipine given orally caused an increase in urine flow rate and a modest but consistent increase in sodium excretion (from 1.0% to 2.2% of filtered load, P less than 0.01). Furthermore, both solute-free water clearance and percentage of free water excreted rose (from 10.1 +/- 0.6 ml/min to 12.0 +/- 0.8 ml/min and from 8.7% +/- 0.5% to 10.5% +/- 1.1%, respectively, P less than 0.05 in each case). In addition, during the peak effect of the drug on sodium and free water excretion, there was no consistent change in either glomerular filtration rate or effective renal plasma flow. Nitrendipine was also phosphaturic and calciuric but did not alter acid excretion. When administered to subjects with hydropenia receiving hypertonic saline infusion, the drug had no effect on solute-free water reabsorption. We interpret these results to indicate that nitrendipine has direct tubular effects on renal electrolyte transport and that the locus of these effects is probably the proximal tubule. Thus, nitrendipine appears to differ from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.