In thirty-two patients with nephrotic syndrome (NS) phytohemagglutinin (PHA)-induced lymphocyte proliferation was studied at various stages of the disease. We demonstrated that lymphocyte transformation during acute exacerbation is markedly decreased, especially if cells are cultured in patient serum. During treatment with steroids PHA-stimulation improves. During full remission all patients showed their maximal lymphocyte stimulation. On the basis of these results and reports from the literature we postulate that patients with the NS have a T cell clone which inhibits the transformation capacity of the remaining lymphocytes through production of a heat stable serum factor. The same or a second factor produced by these lymphocytes could at the same time exert a toxic effect on the glomerular basement membrane.