Differential reactivity for cathepsin D (cath-D) and epidermal growth factor receptor (EGFR) was compared in 102 archival cases of human primary prostatic carcinoma and nine prostate carcinoma metastases by immunohistochemical techniques using commercially available antibodies (Ciba-Corning, Triton Diagnostics Division, Alameda, CA). Western immunoblotting confirmed that the anti-cath-D and anti-EGFR antibodies recognized the appropriate-sized proteins in extracts of human prostatic carcinoma cell lines. For immunohistochemical analysis, the primary prostate carcinomas ranged from Gleason's combined scores of 2 to 9. High-grade prostatic intraepithelial neoplasia was coexistent in 79 of the cases. Immunohistochemical staining was scored by summing the intensity of staining (0 to 3+) weighted by the percentage of tumor staining at each intensity (H score, theoretical range 0 to 300). Heterogenous moderate to strong reactivity with anti-cath-D was detected in 96 of 102 cases of primary prostate carcinoma (94%), with a mean H score of 176.5. EGFR reactivity was much less common and less strong, with 41 of 102 primary prostate carcinomas staining (40%) at a mean H score intensity of 29.2. The immunohistochemical (H) scores of cath-D and EGFR reactivity both significantly correlated with the Gleason's combined score of the tumors. There was no significant correlation between the cath-D and EGFR scores. Ninety-nine percent of the examples of prostatic intraepithelial neoplasia were reactive with anti-cath-D, with no clear correlation between the intensity of staining of prostatic intraepithelial neoplasia and the adjacent carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)