14C-Captopril was given intravenously to four normal subjects in a 4-mg priming dose followed by constant intravenous infusion of 1.7 mg/hr for 3.5 hr with and without concomitant probenecid. Steady-state levels of unchanged captopril were obtained between 1.5 and 3.5 hr. In the presence of probenecid, the average steady-state blood levels of total radioactivity were higher (36%) than on captopril alone. Unchanged captopril levels were slightly higher (14%) in the presence of probenecid. Kinetic evaluations were carried out exclusively on data for unchanged captopril. The average total body clearance (ClT) and renal clearance (ClR) of captopril in the absence of probenecid were 775 and 388 ml/kg/hr. The corresponding values for captopril with probenecid (631 and 217 ml/kg/hr) were lower. The average ratio of ClR to ClT for captopril alone was 0.50 and fell to 0.35 in the presence of probenecid. When captopril alone was given, a minimum of 78% of the renal excretion of captopril during steady-state could be attributed to net tubular secretion, but when captopril was given with probenecid, net tubular secretion was only 56%. The volume of distribution of captopril during steady state was not altered by probenecid. For the first 3.5 hr, cumulative renal excretion of total radioactivity with and without probenecid was 55% and 60%, but cumulative excretion of unchanged captopril was higher after captopril alone (36% of dose) than after the combination (21% of dose).