The administration of calcium-blocking drugs exerts a natriuretic response. Acute studies in isolated perfused kidneys and in experimental animals, as well as in man, consistently demonstrate diuresis, natriuresis, calciuresis, and generally kaliuresis, even in the face of arterial blood pressure reduction. Clearance methodology suggests that calcium-blocking drugs exert their natriuretic response by exerting hemodynamic effects, as well as by acting directly on the proximal tubule. Micropuncture studies and experiments utilizing the toad urinary bladder suggest that calcium-blocking drugs impair sodium reabsorption in the distal tubule. Chronic studies in both animals and man, in which sequential urine collections were made in the face of a known sodium intake, corroborate the natriuretic effects of calcium-blocking drugs. Moreover, these studies suggest that the effects of these medications are likely to be clinically important.