The pathogenesis, prognosis, and reversibility of renal failure were assessed in 494 consecutive, previously untreated patients with multiple myeloma. For patients with a similar extent of disease, the presence or degree of azotemia did not adversely affect prognosis. Hypercalcemia and/or Bence Jones proteinuria explained the renal failure in 97% of patients. After treatment with a combination of hydration and chemotherapy, normal renal function was achieved in 51% of patients, reversibility usually being rapid and occurring more often in those with slight elevation of serum creatinine. Myeloma control was much more important for survival prolongation than reversal of renal failure, supporting the prompt institution of effective therapy for the underlying malignancy.