In five adult patients (aged 44 to 74 years) with idiopathic nephrotic syndrome, irreversible acute renal failure developed. Prior renal disease, associated systemic illness or occlusion of major renal vasculature was not present. All patients continued to excrete large amounts of proteins (8.6 to 15 g/24 hours) despite a minimal glomerular filtration rate and severe oliguria. One patient died after five months without recovering renal function. Four patients have required hemodialysis for a period of 12 to 58 months. The failure to recover renal function could not be explained by the light microscopic findings. It is suggested that the irreversibility of the renal failure may be related to either permanent alterations in renal blood flow or ultrastructural changes, or to both. Clinically, adult patients in whom acute renal failure develops during the course of idiopathic nephrotic syndrome seem to have a grave prognosis. Protracted oliguria or irreversible renal failure can be expected to occur.