We have previously reported that the drs gene has the ability to suppress transformation by v-src and v-K-ras in the rat cell line F2808. We have also shown that the expression of drs mRNA is markedly reduced in a variety of human cancer cell lines, suggesting that down-regulation of drs mRNA is correlated with the development of human cancers. To clarify the role of the drs gene in prostate carcinogenesis, we examined the expression of the drs gene in 3 normal prostate, 13 prostate carcinoma, 5 benign prostate hyperplasia (BPH), and 2 prostatic intraepithelial neoplasia (PIN) tissue specimens by in situ hybridization and in 3 prostate carcinoma cell lines (PC3, LNCaP, and DU145) and 2 BPH tissues by Northern blot analysis. Furthermore, the deletion, and rearrangement of the drs gene were analyzed by Southern blot analysis. The drs mRNA was significantly expressed in normal prostate and BPH tissues, whereas it was markedly down-regulated in prostate carcinoma tissues and prostate carcinoma cell lines. In 2 tissues from PIN, drs mRNA was weakly expressed. There were no differences between prostate carcinoma cell lines and BPH tissues in terms of their banding patterns of Southern blot analysis. These results indicate that down-regulation of drs mRNA is closely correlated with development of prostate carcinoma, suggesting a tumor-suppressor function of the drs gene in this cancer.