Studies using ovarian carcinoma cell lines have suggested that such tumors of epithelial derivation express low levels of receptors for coxsackie-adenoviruses (CARs). To better assess the susceptibility of ovarian carcinomas to these potential viral receptors as targets for gene therapy, we carried out a study in patient material, to measure the proportion and intensity of immunoreactivity to CARs with a monoclonal antibody directed against an unknown epitope on the receptor. Formalin-fixed, paraffin-embedded tissue from 47 cases of ovarian carcinoma were stained by using the avidin- biotin-peroxidase method. Included were 10 endometrioid tumors, 10 serous tumors, 10 mucinous tumors, 10 tumors of extraovarian origin, four clear-cell variants, and three malignant mixed mullerian tumors (MMMTs). The cases were specifically selected to include a representative population across all ages (ages 30-83 years), stages (I-IV), and grades of tumor (I-III). We also examined five endometrioid tumors of endometrial origin to test whether tissue of origin could be differentiated immunohistochemically by using this antibody. Positivity was scored independently by two pathologists by using a two-tiered system consisting of a cellular proportion score and an intensity score. Mimicking the in vitro studies, there was near-universal staining of epithelial ovarian tumors across all types (80% of endometrioid tumors, 70% of serous tumors, 100% of mucinous tumors, 90% of ovarian tumors of extraovarian origin, three of four of the clear-cell variants, and two of three of the MMMTs), although the staining pattern was predominantly weakly positive. Similarly, all five tumors of endometrial origin were positive for CAR. We concluded that though CAR is ubiquitously expressed by epithelial ovarian carcinomas, the staining pattern is predominantly minimally reactive, suggesting a relative paucity of these viral receptors.