Treatment of patients with membranous glomerulonephritis with prednisone on alternate days results in a decreased proteinuria on non-prednisone days. We have studied this phenomenon in more detail in 14 patients (11 M, 3 F) with membranous glomerulonephritis. Mean age +/- SD of the patients was 47 +/- 14 years, mean endogenous creatinine clearance 94 +/- 35 ml/min, and median proteinuria 8.8 g/24 h (range 5.0-30.0 g/24 h). Glomerular filtration rate (GFR, inulin clearance), effective renal plasma flow ERPF, PAH clearance), and proteinuria were measured on a control day (C), and six days after the start of alternate-day prednisone treatment, on the third non-prednisone day (NP3, 24-28 h after the last dose of prednisone). Proteinuria decreased from 6.1 mg/min (3.2-9.8 mg/min) (C) to 2.5 mg/min (1.0-7.7 mg/min) at NP3 (median, interquartile range; P less than 0.01), the percentage decrease averaged 45 +/- 8%. The decrease of proteinuria was correlated with baseline GFR (r = 0.75; P less than 0.01). GFR and ERPF did not change significantly, but filtration fraction decreased significantly from 14.5 +/- 0.8% (C) to 13.5 +/- 0.9% (NP3; P less than 0.05). Fractional excretion of albumin, IgG, and transferrin decreased significantly, by -40 +/- 8%, -52 +/- 6%, and -52 +/- 7% respectively. Fractional excretion of beta 2-microglobulin decreased significantly less by -12 +/- 10%. We conclude that proteinuria is decreased on non-prednisone days in patients with membranous glomerulonephritis treated with alternate-day steroids. The observed decrease of filtration fraction suggests that a reduction of glomerular pressure is involved. In addition, the magnitude of the decrease of proteinuria might indicate a change in glomerular permselectivity characteristics.