As part of a study on the interaction between diuretics and renal prostaglandins, four healthy medical students receiving indomethacin for 8 days were also given triamterene for 3 days. Whereas renal function was initially normal in all four subjects, creatinine clearance decreased in two by 62% and 72% after concomitant administration of the two drugs, and was only restored to normal after 4 weeks. In control periods when triamterene or indomethacin was given alone renal function was preserved in all subjects. Urinary prostaglandin E2 was stimulated by triamterene and inhibited by indomethacin in all four subjects; both changes were more marked in the two sensitive subjects. Thus prostaglandin inhibition by indomethacin may unmask triamterene toxicity and contribute to the pathogenesis of the renal failure observed in sensitive subjects. As alternative therapy is readily available, avoidance of this potentially nephrotoxic association is recommended.