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Production of immun0reactive (it-) endothelin-2 (ET-2) in renal adenoearcinoma cells, ACI IN, was reduced by transforming growth factor-fl, basic fibroblast growth factor, transforming growth factor-at and, most strikingly, by epidermal growth factor (EGF). These growth factors did not show such inhibitory effects on the secretion of ir-ET-I in ET-l-producing cells, indicating that the production of ET-2 and ET-I is regulated differently by the growth factors. EGF specifically reduced the sacra :on of not only ir-ET-2 but also ir-big ET-2 with only a small decrease in total protein synthesis. Northern blot analysis indicated that EGF controls the ET-2-production at the transcription levels of ET-2 gene.