The roles of the renin-angiotensin system (RAS) and aldosterone in the pathogenesis of nephrotic syndrome were investigated with rats following subcutaneous injections of puromycin aminonucleoside (PAN) for 7 d. Prominent reduction in plasma renin activity (PRA) was observed at day-15 after the initial treatment with PAN preceded by the onset of the nephrosis and there was no significant difference in plasma aldosterone concentration (PAC) between the nephrosis and normal control groups despite the higher levels obtained in the nephrosis animals. Although we could not elucidate the precise mechanism of reduction in PRA, it was suggested that neither the RAS nor aldosterone secretion played a primary role in the pathogenesis of the nephrosis. PAN-induced nephrosis is interesting in studying the pathophysiological mechanism of the lowered activity of plasma renin in some patients with nephrotic syndrome.