Atrial natriuretic peptide (ANP) increases proteinuria in primary glomerular disease. To study whether mesangial proliferation influences this effect, we infused α-human ANP at 25 ng/kg/min for 40 min into 6 patients with minor glomerular abnormalities (MGA), 10 with focal glomerulonephritis (FGN) and 8 with diffuse glomerulonephritis (DGN), and determined its renal effects. ANP significantly increased urinary excretions of Na and protein in all groups. Increases in urinary Na excretion were comparable among the groups (about + 200%), while increases in urinary protein excretion were greater in DGN than in the other two groups (DGN +153 μg/min/1.73 m<sup>2</sup>, MGA + 77 μg/min/1.73 m<sup>2</sup>, FGN +70 μg/min/1.73 m<sup>2</sup>). This increase was not related to the preinfusion level of proteinuria. Furthermore, the ratio of urinary protein to creatinine was significantly elevated by about 250% in the three groups. Thus, ANP seems to increase the permeability of the glomerular basement membrane to protein, particularly in patients with DGN, possibly through mesangial proliferation and the associated changes in adjacent tissues.