Overexpression of the neu oncoprotein has been described in several tumor models including breast and prostate cancer. Overexpression of neu has been reported to have prognostic significance in certain tumors but controversy continues regarding the role and frequency of neu overexpression in prostatic cancer. The objectives of the study were twofold. First, to characterize neu expression in prostate cancer in comparison to benign prostatic hyperplasia. Second, to determine whether neu expression correlates with Gleason grade in prostate cancer. Thirty-nine prostate cancers obtained from radical prostatectomy specimens and 10 benign prostatic hyperplasia specimens were included in the study. Specimens were formalin fixed and paraffin-embodied. neu expression was studied by immunohistochemical staining using a monoclonal neu specific AB-3 antibody. All 39 specimens (100%) of prostate cancer showed positive immunostaining of variable degree while 2 (20%) benign prostatic hyperplasia specimens showed positive staining. Thus, neu oncogene is overexpressed in localized prostate cancer compared to benign prostatic hyperplasia. The degree of neu immunostaining did not correlate with Gleason grade and there appeared to be a tendency towards an inverse relationship. The prognostic significance of the varying overexpression is unknown.