1. The clinical manifestations, laboratory data and renal histologic features of acute renal failure occurring in 14 patients with multiple myeloma are reviewed and contrasted with the data from 29 previously reported cases. 2. Whereas other reports have stressed the role of intravenous pyelography and dehydration in the development of acute renal failure in multiple myeloma, the most common etiologic factor in our experience was hypercalcemia (7 patients). Other factors included potentially nephrotoxic antibiotics (3 patients) and volume depletion (2 patients). Intravenous pyelography could be clearly implicated in ony one patient. 3. The unusually high incidence of Bence Jones proteinuria in these patients is consistent with the possibility that Bence Jones protein excretion is associated with an increased susceptibility to renal injury. This could be due to an adverse effect of Bence Jones proteins on the renal tubules or their tendency to precipitate in tubular lumina during periods of reduced tubular flow. 4. The prognosis of patients with multiple myeloma who develop acute renal failure is poor; only 5 of our 14 patients survived the early period of acutely impaired renal function, and 4 of these subsequently died within 2 months. Preventive measures particularly the prompt correction of hypercalcemia and volume depletion, are the most important aspects of patient management.