Flow cytometric analysis of nuclear DNA ploidy pattern was performed on 91 samples of prostatic adenocarcinoma from patients with stage D1 disease (metastatic deposits in pelvic lymph nodes). All patients had undergone radical retropubic prostatectomy and bilateral pelvic lymphadenectomy. Clinical follow-up ranged from 5 to 19 years. Nuclei were extracted from paraffin-embedded archival material. Isolated nuclei were stained with propidium iodide. The DNA ploidy pattern was diploid (normal) in 42% of tumors, tetraploid in 45%, and distinctly aneuploid in 13%. Only 15% of DNA diploid tumors progressed locally or systemically, whereas 75% of tumors with an abnormal DNA ploidy pattern (tetraploid or aneuploid) subsequently progressed (P<0.0001). Among low-grade tumors, ploidy analysis detected a subgroup associated with a poor prognosis; among high-grade tumors, a subgroup associated with a favorable prognosis was detected. None of the patients with a DNA diploid tumor died of prostatic cancer during the period of observation. In contrast, 43% of patients with DNA tetraploid tumors and 44% of those with DNA aneuploid tumors had died of prostatic cancer 10 years after surgical treatment (P<0.001). Determination of nuclear DNA ploidy pattern by flow cytometry provides objective, highly significant, prognostic information for patients with stage D1 prostatic carcinoma.