Epithelial ovarian tumors of varying malignancy as well as normal ovaries were examined for their expression of p53 with the monoclonal antibody PAb1801. Immunohistochemical detection of p53 protein is possible when the gene has been mutated, but not when the normal gene product alone is present. Our results indicate that this tumor suppressor gene may be involved in tumorigenesis, as its expression was detected in both borderline and malignant tumors while normal ovaries and benign ovarian tumors were unstained with the p53 antibody. The presence of p53 was also related to dissemination of disease, residual tumor bulk, and poor differentiation as well as the presence of the proliferation variable Ki-67, another negative prognostic variable. No significant relation could be detected to S-phase fraction or DNA ploidy. Furthermore, the presence of p53 in malignant epithelial ovarian tumors was related to significantly decreased patient survival, with only 36% alive compared to 70% in the p53-negative group (P = 0.002). In the subgroup of patients with residual tumor burden after surgery, those with p53-positive tumors had a significantly (P = 0.05) decreased survival compared to those with p53-negative neoplasms, which further supports an independent role in ovarian cancer malignancy.