The renal effects of aspirin and acetaminophen are minor. With a major overdose of acetaminophen, uncommonly renal failure may occur that cannot be ascribed to hepatic failure; its mechanism is unknown. Aspirin may cause a transient shedding of renal tubular cells, alterations in urate excretion, inhibition of spironolactone action, and, in certain clinical settings, a reversible decline in renal function manifested as a fall in glomerular filtration that may be accompanied by mild water, sodium, and potassium retention. Active systemic lupus erythematosus, advanced cirrhosis, and chronic renal insufficiency seem to predispose patients to the effects on renal function, and there is direct or indirect evidence in those conditions that prostaglandin synthesis is an important part of the body's attempt to preserve renal blood flow. Study of these effects has provided new insight into the way in which the kidneys may use prostaglandins to preserve renal function when it is threatened.