1. We found that adrenocorticotrophic hormone (ACTH) release in rats induced by acute swimming exercise or by an intravenous injection of human recombinant interleukin-1 beta (IL-1 beta) was significantly attenuated after chronic exercise. 2. Since involvement of prostaglandins in the ACTH response induced by IL-1 is well known, we investigated the effect of indomethacin, an inhibitor of prostaglandin synthesis, on the ACTH response induced in rats by acute swimming exercise. Pretreatment with an intravenous injection of indomethacin significantly suppressed the ACTH response induced by exercise. The effect of indomethacin (1 and 10 mg/kg) on the ACTH response was dose-dependent. 3. The effect of chronic exercise on the exercise-induced changes in the plasma concentration of prostaglandin E2 was investigated. The plasma concentration of prostaglandin E2 significantly increased after acute exercise in both the control and the chronically exercised rats. However, the increase in the plasma level of prostaglandin E2 was significantly smaller in the chronically exercised group than in the control group. 4. Intravenous injections of prostaglandin E2 produced dose-dependent increases in the plasma concentration of ACTH in rats. 5. The present results suggest that an increase in prostaglandin E2 levels in plasma is involved in the development of the ACTH response induced by exercise.