Clinical studies with intraperitoneal nitroprusside were designed to examine drug effects on peritoneal clearances as a function of dose, frequency of administration and dwell times. Increases in clearances and protein losses were seen with 1 mg of nitroprusside per liter of dialysis solution, with progressively greater effects up to maximum doses of 4.5 mg/l.Maximum effects were seen at the high dose after 3 or more consecutive exchanges. Clearance effects promptly returned toward control during postdrug exchanges and, in some studies, even during alternate exchanges. Proportional effects on solute clearances appeared independent of dwell time, supporting previous studies suggesting area permeability alterations. Series of 12 or more consecutive exchanges showed little change in blood pressure. Increases in serum thiocyanate were not detected after multiple exchanges. Dialysate cell counts showed no evidence of chemical irritation.