Mullerian inhibiting substance (MIS) was investigated for its ability to inhibit growth of a human ovarian cancer in nude mice. Biologically active preparations from newborn calf testes, obtained after sequential ion exchange chromatography, delayed or prevented growth of a human ovarian cancer (HOC-21) when 2 X 10(6) cells were preincubated with them prior to subcutaneous injection of the tumor cells into Balb/C homozygous nude mice. Preincubation of a human colon carcinoma cells (SW-48) with similar preparations of MIS failed to inhibit growth of the tumor cells in nude mice. Human serous carcinomas are thought to arise from the ovarian surface epithelium, a derivative of the coelomic epithelium of the urogenital ridge, which invaginates to form the mullerian duct early in embryonic life. The neoplastic cells of serous tumors simulate morphologically the lining cells of the fallopian tube, which are derivatives of mullerian duct epithelium. This study provides physiologic confirmation of the mullerian nature of this type of tumor and suggests that MIS may ultimately prove to be effective in its therapy.