1. The effect of 3 days' treatment with indomethacin on the renal response to infused vasopressin was assessed in eight healthy volunteer subjects.
2. Indomethacin produced significant weight gain and an increase in serum potassium without a change in creatinine clearance.
3. Although indomethacin reduced maximum free water clearance in five subjects, the antidiuresis produced by an incremental infusion of physiological amounts of vasopressin was no different whether indomethacin had been taken or not.
4. Indomethacin, in the dose we have used, is known to reduce prostaglandin production and we therefore conclude that endogenous prostaglandins do not inhibit the effect of physiological amounts of vasopressin on water clearance, which makes it unlikely that prostaglandins are important in the day-to-day modulation of the response to vasopressin.