A study was carried out to assess the prognostic significance of significance of p53 expression in ovarian tumors. Archival material from 105 ovarian cancer biopsies was examined for the presence of the p53 protein by an immunoperoxidase technique using the cell-mediated immune (CMI) antibody. Employing a 3-point scale for intensity and the proportion of malignant cells positive, 26% of cases had a score of 4 to 6, 19% were 1 to 3, and 55% were negative. There was no correlation with response to therapy or survival at a median follow-up of 6 years, but a higher score was found to correlate with poor tumor differentiation (Spearman rank: p = 0.03). In a more recent series of 38 ovarian cancer patients, serum autoantibodies to the p53 protein were detected in 29% of cases by an ELISA technique compared with 1 out of 73 normal control women. In 19 of these cases, both serum and malignant tissues were negative, while in 7 of the 11 cases with positive sera, the tissue was also found to contain detectable p53 protein. We conclude that tissue expression of p53 in ovarian tumors is associated with poor histological differentiation and the presence of detectable serum autoantibodies.