Captopril decreases protein excretion in patients with nephrosis. To evaluate whether captopril has an acute antiproteinuric effect and to evaluate the role of changes in renal hemodynamics or glomerular permselectivity on this effect, renal clearance studies were performed in patients without diabetes but with nephrosis. Protein excretion and renal hemodynamics were measured at baseline and after the administration of captopril. To measure the contribution of renal prostaglandins, patients were restudied on a separate day, after the combined administration of captopril and the prostaglandin synthetase inhibitor ibuprofen. Both treatments significantly reduced mean protein excretion, but the change was greater with combined therapy than with captopril alone (40.6% vs 20.0%). Mean glomerular filtration rate (GFR) decreased by 4.8% (not significant) and 16.5% (p < 0.001), and filtration fraction (FF) decreased by 13.6% (p < 0.001) and 14.9% (p < 0.001) after captopril alone and combined therapy, respectively. No significant correlation was found between changes in proteinuria and changes in GFR or FF after treatment with captopril alone. In contrast, the decrease in proteinuria correlated with the change in GFR after combined drug administration (r = 0.68, p = 0.06). The ratio of immunoglobulin G to albumin clearance, an index of glomerular permselectivity, was unaffected by captopril but decreased significantly (by 43%) after combined drug administration. The results suggest that the acute antiproteinuric effect of captopril is not due to changes in FF, GFR, or glomerular perselectivity. The addition of ibuprofen enhances the antiproteinuric effect of captopril by decreasing the GFR as well as by enhancing the permselectivity of the glomerular capillary membrane. © 1990.