The effects of endothelin (ET) 1 on the release of somatostatin (SS) and thyrotropin-releasing hormone (TRH) from the rat stomach were studied in vitro. The rat stomach was incubated in medium 199 with 1.0 mg/ml of bacitracin (pH 7.4) for 20 min. The amounts of SS and TRH released into the medium were measured by individual radioimmunoassays. With the addition of ET-1, the release of SS from the rat stomach was inhibited significantly in a dose-related manner, whereas TRH released from the stomach was enhanced significantly. These effects of ET-1 on SS or TRH release were blocked by BQ-485, a blocker of ETA receptor. These findings suggest that ET-1 inhibits SS and stimulates TRH release from the rat stomach in vitro, and that these effects are mediate via ETA receptor.