Adrenocorticotropic hormone (ACTH) and mouse but not human interferon caused a steroidogenic response and induced antiviral activity in mouse adrenal tumor (Y-1) cells. ACTH and human but not mouse interferon caused induction of melanin synthesis and antiviral activity in human melanoma cells. ACTH did not induce antiviral activity in mouse L or human amnion (WISH) cells. The hormonal activities of interferon were neutralized by specific rabbit anti-interferon sera. Thus, interferon has species-specific hormonal activity and ACTH has cell-specific antiviral activity. These results are discussed in terms of the possible natural functions of interferon and polypeptide hormones. © 1981 Springer-Verlag.