We investigated whether platelets, which are rich in growth factors, could mediate glomerular cell proliferation in immune complex glomerulonephritis (GN) in the rat induced with an antibody directed against the Thy-1 antigen present on mesangial cells. Rats were depleted of platelets (mean platelet count less than 20,000/mm3) with goat anti-rat platelet IgG before induction of GN and platelet depletion was maintained for 48 hours. At 72 hours sections were immunostained for cyclin, an S-phase-related nuclear antigen, to identify proliferating cells, and for the common leukocyte antigen (CD45) to identify infiltrating leukocytes. Platelet depleted rats had fewer proliferating resident glomerular cells (CD45-, cyclin+) compared to controls (0.8 +/- 0.5 vs. 2.8 +/- 1.4 cells/glom cross section, P less than 0.01) and better renal function (creatinine 1.07 +/- 0.12 vs. 1.27 +/- 0.15 mg/dl, P less than 0.05). These effects were not due to changes in circulating or glomerular leukocyte counts, complement, or glomerular antibody binding. These studies provide the first direct evidence that platelets mediate glomerular (probably mesangial cell) proliferation in antibody-mediated GN.