p53 protein accumulation in the nuclei of prostatic carcinoma cells, as detected by immunohistochemistry, has been associated with increased cell proliferation rate, increased histologic grade and stage, androgen independence and decreased patient survival. Little is known, however, of p53 in prostatic intraepithelial neoplasia (PIN), the putative precursor proliferation for moderately to poorly differentiated peripheral zone carcinoma of the prostate. In this investigation, we utilized a panel of antibodies reactive with p53 protein to assess p53 protein accumulation in prostatic epithelial hyperplasia, PIN and prostatic carcinoma. Forty patients who had undergone radical prostatectomy were selected for study based on the presence of high grade PIN and carcinoma in the same prostate tissue block. Tissue sections were treated with microwave irradiation for antigen retrieval, and antibodies DO-7, PAb1801 and CM-1 were used for immunohistochemical analysis. An intense signal for immunoreactive p53 was identified in the nuclei of 7/40 (17.5%) clinically-localized prostatic carcinomas. In all 7 cases, high grade PIN also exhibited intense p53 immunoreactivity, whereas only one case of hyperplasia contained immunoreactive p53 protein. These findings support a close relationship between high grade PIN and carcinoma in a subset of primary prostatic carcinomas with high-level p53 protein accumulation.