It has been suggested that minimal-change nephropathy (MCN) may be related to a disorder of cell-mediated immunity. Lymphocyte cell-surface markers (E and EAC rosettes) and functional markers (mitogenic response to PHA, Con A and PWM) were examined in 13 patients with MCN and nephrotic syndrome (NS) and in 13 patients with MCN in remission compared to 20 patients with membranous glomerulonephritis (MG) and NS, and 20 normal controls. None of the patients received medication at the time of the study. The response to various mitogens of MCN with NS was significantly reduced, while MCN in remission and MG had mean values of the mitogenic response not significantly different in respect to normal controls. Lymphocyte hyporeactivity in autologous plasma was associated, in approximately 50% of the patients with MCN and NS, to a normal lymphocyte response in homologous plasma and to the presence of an inhibitory effect of MCN plasma on normal lymphocytes. Also, the percentage of E rosettes was reduced, while the percentage of EAC rosettes was increased. The defect of T cells was not related to the degree of the NS. In 7 patients, studied at the onset of NS and afterwards in remission, the functional and numerical lymphocyte deficit disappeared during recovery. There is evidence that MCN is associated with a functional disorder of T cells which may be related to the presence of a humoral inhibiting factor.