OC125, a murine monoclonal antibody, recognizes an antigenic determinant (CA125) that is associated with greater than 80% of epithelial ovarian neoplasms of serous, endometrioid, clear cell, and undifferentiated types. In the present report, a sensitive biotin-avidin immunoperoxidase technique was used to determine reactivity of OC125 with normal adult and fetal tissues, as well as with neoplasms of nonovarian origin. In fetal tissues, the antibody reacted with amnion and with derivatives of the coelomic epithelium, i.e., the müllerian epithelium and the lining cells of the peritoneum, pleura, and pericardium. Among adult tissues, OC125 reacted with the epithelium of fallopian tubes, endometrium, and endocervix. The CA125 determinant was also detected on mesothelial cells in the adult pleura, pericardium, and peritoneum, particularly in areas of inflammation and adhesion. Curiously, the surface epithelium of normal fetal and adult ovaries, thought to be derived from coelomic epithelium, did not express the determinant, except in inclusion cysts, areas of metaplasia, and papillary excrescences. Of neoplastic tissues of nonovarian origin, OC125 reacted consistently only with adenocarcinomas of the endocervix, endometrium, and fallopian tube, and with mesotheliomas. Only seven of 64 nongynecological tumors tested reacted with OC125. Thus, OC125 detects a differentiation antigen shared by fetal coelomic epithelium and its derivatives in the fetus and the adult. Apparently, this antigen disappears early in the course of formation of the ovarian epithelium and is reexpressed in certain reactive and neoplastic lesions, a process that could be termed "molecular metaplasia."