The etiology of acute renal failure has changed in recent years due to the recognition of drug nephrotoxicity as a more common cause. In this communication we emphasize recent information concerning the pathophysiology of nephrotoxic acute renal failure produced by aminoglycoside antibiotics and the contrast media used in roentgenography. The aminoglycosides are excreted primarily by glomerular filtration; however, net tubular reabsorption and renal parenchymal accumulation do occur. The exact mechanism of uptake is not clear, but the luminal membrane seems primarily involved. The pathogenesis of nephrotoxicity, although probably linked to cortical accumulation, is complex since experimental animals recover from gentamicin-induced renal failure despite continued administration of the drug. Knowledge of the precise cellular mechanisms of injury awaits further studies. Histologic damage is usually limited to proximal tubular necrosis and, clinically, the renal failure is nonoliguric. Although reports of the contrast media used in roentgenography producing acute renal failure have increased, the pathogenesis is unclear. Evidence supporting various theories is reviewed.