A murine monoclonal antibody (MAb 12C3) that is specific to human ovarian carcinomas was generated by immunizing mice with a human ovarian germinoma cell line (JOHYC-2). The antigen distribution that was defined by MAb 12C3 in normal and malignant human tissues was analyzed by immunohistochemistry on paraffin-embedded and frozen sections. The antibody reacted with 67.7% (21 of 31 cases) of epithelial ovarian carcinomas (6 of 12 cases of serous cystadenocarcinoma, 5 of 7 cases of mucinous cystadenocarcinoma, 7 of 9 cases of clear cell carcinoma, 3 of 3 cases of endometrioid adenocarcinoma), but did not react with any of the benign epithelial ovarian adenomas tested. Partial regions of borderline ovarian malignancies that exhibited marked papillary projection of the lining cells with cellular atypia reacted positively with MAb 12C3 in 14 of 25 cases (56.0%). The histologic features of regional early malignant change corresponded to the expression of the MAb 12C3 epitope in the borderline malignant tumor cells. There was a low frequency of reaction (4.3%) between the antibody and other gynecologic and nongynecologic malignancies (46 cases of 12 tissues). In normal tissues, the antibody reacted positively with only three tissues, including corpora lutein cells, excretory ducts in the submandibular gland, and basal cells of the sebaceous glands. The antigen epitope defined by MAb 12C3 was present on a glycoprotein with a molecular mass of 200 kDa and did not exhibit any cross-reactivity with other well-known tumor markers. These data suggest that MAb 12C3 may be a useful tool for the immunohistologic detection of early malignant changes in epithelial ovarian tumors. In addition, MAb 12C3 also may facilitate a differential diagnosis between benign and borderline malignancies.