This study evaluates the direct effects of verapamil (5 micrograms/kg/min) or nifedipine (0.32 micrograms/kg/min) when infused into one renal artery for 2 h. The role of calcium in the systemic and renal vascular effects of angiotensin II (1 microgram/i.v. bolus) was examined in each period. Renal blood flow was increased 11% by verapamil and 29% by nifedipine. Unlike other vasodilators, these drugs markedly increased GFR (by 75% with verapamil and 50% with nifedipine), and both caused a profound natriuresis, which outlasted the renal hemodynamic changes. Further, they abolished the renal vascular responses to angiotensin II. These major direct effects on renal function and hemodynamics suggest that: (a) calcium blockers may affect the determinants of GFR differently from other vasodilators, and (b) they may interfere with proximal tubular Na+ transport.