This study investigated the immunohistochemical staining characteristics of glutathione-S-transferase (GST) alpha, pi, mu, and theta in prostatic acinar adenocarcinoma (PCA), prostatic intraepithelial neoplasia (PIN), and benign prostatic tissues from 19 patients. Relationships between GST isoenzyme expression in benign, PIN, and PCA tissue were examined by the Wilcoxon signed-rank test and clinicopathological data were examined by the Spearman correlation rank test. When the benign, PIN, and PCA tissues from these cases were compared according to their staining intensity, GST alpha, pi, mu, and theta expressions in tumor cells were significantly lower than in benign epithelial cells (P<0.05). The GST alpha class displayed the lowest level of expression in PIN and PCA. Expression of GST pi was lower in PCA tissue than in PIN and benign epithelial tissue (P<0.05). We hypothesize that carcinogenesis in the prostate results from impaired cellular handling of mutagenic agents owing to reduction or loss of expression of multiple GST isoenzymes and other detoxifying and antimutagenesis agents. This study confirms the down-regulation of GST isoenzymes in PCA of the prostate and shows that the loss of GST isoenzyme expression is a phenotype associated with malignant transformation. There was no statistical relationship between GST isoenzyme expression and the clinicopathological data (age, Gleason score, and total serum prostate-specific antigen levels) (P>0.05).