OBJECTIVE To evaluate the relationship between the nuclear DNA content and the tissue estrogen receptor (ER) level in patients with operable adenocarcinoma of the prostate. METHODS Surgical specimens taken from 73 patients with clinically localized prostate cancer were studied. Tumor DNA ploidy pattern as measured by flow cytometry was correlated with the level of functional ER using the nuclear biopsy assay. RESULTS Forty-five percent of the tumors were DNA diploid, and 55% had an abnormal ploidy pattern (DNA tetraploid or DNA aneuploid). The ER level ranged from 0 to 6,475 fmol/mg DNA (mean 839 fmol/mg DNA). Twenty-two percent had no functional receptors. Marked association was noted between ER and nuclear DNA content. Seventy-five percent of the tumors with no ER had abnormal ploidy patterns. The mean receptor level for DNA diploid prostate cancer was 1,034 fmol/mg DNA versus 661 fmol/mg DNA for DNA nondiploid tumors (p < 0.008). An inverse correlation was found between ER values and histologic grade or pathologic stage. High-grade and high-stage tumors had lower levels of ER compared to low-grade and early-stage carcinomas. CONCLUSIONS Our results demonstrate an association between ER values and variables that predict prognosis in prostate cancer. It is possible that this parameter may be helpful in identification of prognostic groups in patients with prostate cancer.