Supernatants of peripheral blood mononuclear cell culture from children with minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) were tested for their ability to increase glomerular basement membrane (GBM) permeability and for effects on anionic sites in the GBM. Supernatants from cultures of concanavalin A-stimulated peripheral blood mononuclear cells from patients with MCNS, those with FSGS and normal controls were infused into the renal arteries of normal rats. Infusion of the supernatants from patients with MCNS and FSGS caused a significant reduction of anionic sites in the GBM (p < 0.001) and a significant increase in urinary albumin excretion (p < 0.05), whereas infusion of supernatants in control cases did not reduce anionic sites nor increase urinary albumin excretion. These findings show that stimulation of peripheral blood mononuclear cells from MCNS and FSGS with concanavalin A results in liberation of soluble substances which reduce polyanions in the GBM and increases GBM permeability.