We studied the effect of serum from patients with renal diseases characterized by mesangial proliferation on the proliferation of rat mesangial cells (MC) in culture. Indirect immunofluorescence technique with human anti-proliferating cell nuclear antigen (PCNA) antibody was utilized to detect proliferating MC in S-phase on microscope slides. MC from serum-starved culture medium containing 0.5% fetal calf serum (FCS) showed 6 +/- 2% of PCNA-positive MC, whereas those from complete medium containing 20% FCS showed 45 +/- 7%. This was confirmed by flow cytometry for MC from both conditions, in which 10.9% and 55.2% of S-phase MC were detected, respectively. Serum from 17 patients with IgA nephropathy as a prototype of mesangial proliferative glomerulonephritis produced more PCNA-positive MC than serum from 18 healthy controls (mean +/- S.D. = 21.5 +/- 9.9% vs. 4.4 +/- 5.9%, p < 0.001). In IgA nephropathy, this effect correlated tentatively with active histologic lesion in the glomeruli, but not with severity of urinary abnormalities. Serum from membrano-proliferative glomerulonephritis (MPGN) also produced significant PCNA-positive MC (mean +/- S.D. = 15.6 +/- 9.3%), compared to controls (p < 0.01), independent of the severity of urinary abnormalities. These findings suggest that serum effect on the proliferation of cultured rat MC may reflect an active histologic lesion in the glomeruli, and that anti-PCNA antibody to detect proliferating MC is, if not quantitative, relevant methodology to enumerate proliferating MC in culture.