In patients with a nephrotic syndrome administration of prednisolone causes an increase of proteinuria. To elucidate the mechanism of this effect we have studied the acute proteinuric effect of prednisolone, 125 to 150 mg intravenously, in nine patients (7 M, 2F) with a nephrotic syndrome. Mean age (+/- SD) of the patients was 53 +/- 6 years, mean endogenous creatinine clearance 104 +/- 30 ml/min, and mean proteinuria 7.7 +/- 3.0 g/24 hr. After administration of prednisolone, urinary total protein excretion rose in all patients from a mean (+/- SEM) of 4.89 +/- 0.59 mg/min before to 9.09 +/- 0.99 mg/min at five hours after administration (P less than 0.01). Glomerular filtration rate (inulin clearance), effective renal plasma flow (PAH clearance), and filtration fraction did not change significantly. The increases of urinary excretion of albumin (median %: +92%), IgG (median %: +88%), and transferrin (median %: +76%) were comparable and correlated significantly. Urinary excretion of beta 2-microglobulin did not change significantly however. We conclude that intravenous administration of prednisolone to patients with a nephrotic syndrome causes an increase in urinary protein excretion rate which cannot be explained by changes in renal hemodynamics or tubular protein reabsorption, and which therefore must be the result of a change in glomerular permselectivity characteristics.