A murine monoclonal antibody, OC125, reacts with a surface component of ovarian tumor cells from humans, but fails to react with normal adult ovarian cells. The spectrum of reactivity of OC125 in ovarian tumors from humans was defined by testing cryostat tissue sections from 60 selected ovarian tumors by indirect immunofluorescence. OC125 stained 7/7 benign, and borderline serous ovarian tumors, 19/23 (83%) serous adenocarcinomas, 2/2 mixed serous and endometrioid carcinomas, 2/3 endometrioid carcinomas, 1/4 clear cell carcinomas, and 2/2 undifferentiated carcinomas. No reactivity was found in eight mucinous ovarian tumors or any of the other 11 epithelial sex cord, germ cell, on hematopoietic tumors tested. In neoplastic cysts, papillae, and glands, the staining was most intense on the luminal surface or in subjacent cytoplasm. Cells in solid sheets also showed peripheral staining. Within a reactive tumor, both negative and positive cells could be found, intimately intermixed. There were no differences in these staining patterns between tissues from primary and metastatic sites. The expression of the OC125 antigen was not related to the degree of malignancy as judged by pathologic criteria. Although mucinous tumors lacked reactivity with OC125, seven of eight mucinous adenomas and adenocarcinomas bound a monoclonal antibody against carcinoembryonic antigen (CEA). Thus, OC125 recognizes a common antigen in some but not all ovarian tumors of serous, clear cell, endometrioid, or undifferentiated type. OC125 may prove useful in the pathologic and cytologic identification of certain types of ovarian tumor cells. Its lack of reactivity with mucinous tumors suggests these belong in a distinct subgroup of ovarian epithelial tumors.