Peripheral blood mononuclear cells (PBMC) from patients with minimal-change nephrotic syndrome (MCNS) were tested for their ability to produce a factor which increases the urinary protein excretion levels of rats. It was shown that enhanced proteinuria can be produced in 8-hour urine specimens from rats by the injection of concentrated supernatants of cultured concanavalin-A-stimulated PBMC of patients with MCNS, but not from other nephrotics or normal subjects. The increase in urinary protein excretion was associated with a significant alteration of glomerular epithelial cells similar to that seen in MCNS. These results suggest that in MCNS, PBMC release a factor, which we termed a glomerular permeability factor (GPF), causing changes in glomerular permeability with resulting proteinuria.