We studied the effect of prednisone on urinary protein excretion in 19 patients with a nephrotic syndrome, who were treated with prednisone (125-150 mg) on alternate days. We found a typical, fluctuating pattern of proteinuria resulting from an increased protein excretion rate on prednisone days and a decreased protein excretion rate on nonprednisone days. The urinary protein excretion on prednisone days was 9.9 +/- 3.3 g/24 h, as compared to 5.7 +/- 3.8 g/24 h on nonprednisone days (mean +/- SD). In the whole group of patients the percentual change in proteinuria was significantly correlated with the endogenous creatinine clearance. However, systematic differences between creatinine excretion rates on prednisone and nonprednisone days were not found in individual patients. In 6 patients, renal hemodynamics were studied more precisely, using a single injection technique. Only a slight and nonsignificant decrease in glomerular filtration rate was found on nonprednisone days (delta = -9.6 +/- 16.3%; mean +/- SD). Filtration fraction remained unchanged. It is therefore suggested that the effects of prednisone on proteinuria are not simply mediated by overall changes in renal hemodynamics.