In vivo and in vitro findings have shown that plasma of patients with idiopathic nephrotic syndrome (INS) contain factors that increase glomerular permeability to proteins. The effects of these factors on proteoglycan synthesis by glomerular cells are unknown. To investigate the effect of plasma from patients with INS (n = 23) and other glomerulopathies (n = 12) on the amount of proteoglycans synthesized by cultured rat mesangial cells and human glomerular epithelial cells, glomerular cells were cultured for 24 h with plasma from patients or control subjects, and incorporation of Na235SO4 in chondroitin dermatan sulfate and heparan sulfate was assessed using a cationic nylon membrane. The mean ratio of glycosaminoglycan produced by rat mesangial cells when in contact with plasma (5%) from INS patients to the amount produced when in contact with control plasma was 0.70 ± 0.06. The mean ratio of heparan sulfate was 0.58 ± 0.08. The decrease of heparan sulfate production was present in the cellular and in the extracellular fraction. It was observed when the cells were in contact with plasma from patients in relapse but not when in remission. No decrease of heparan sulfate production was observed with four of the five patients with membranous glomerulonephritis(ratio of 1.27 ± 0.03), IgA nephropathy (n = 5, ratio of 1.27± 0.03), and membranoproliferative glomerulonephritis (n = 2, ratio of 1.39 ± 0.34). When human glomerular epithelial cells were exposed to 5% plasma from INS patients in relapse (n = 9), the mean ratio of heparan sulfate was 0.62 ± 0.06 in the cellular fraction and 0.72 ± 0.08 in the medium. When in contact with plasma from patients in remission, no difference of glycosaminoglycan production was observed. A factor present in plasma from patients with INS during initial episodes or relapses is able to decrease the proteoglycan production of glomerular cells.