The NM23 gene family (nm23-H1 and nm23-H2) has been reported as a measure of metastatic potential. The goal of this study was to discriminate nm23-H1 and nm23-H2 gene expression in benign and malignant human prostate tissue and to determine the relationship of their expression to tumor stages. Specimens included 5 benign prostatic hyperplasias (BPH), 11 primary prostate adenocarcinomas (CaP) (5 stage B, 5 stage C and 1 stage D1), 2 pelvic lymph nodes with metastases and 3 prostate cancer cell lines derived from metastatic lesions. Polymerase chain reaction analysis of mRNA (RNA/PCR) was used to amplify transcripts of both NM23 genes and a normalizing gene (c-N-ras) to determine the relative levels of expression. A significant difference was shown between the BPH specimens and the cell lines from metastatic prostate cancer for nm23-H2 expression (p = 0.037) and the nm23-H1/nm23-H2 gene expression ratio (p = 0.037). The nm23-H1/nm23-H2 ratio increased significantly (p = 0.026, tau-b = 0.377) from BPH, through the CaP stages, to the cell lines. The expression of nm23-H2 decreased significantly (p = 0.002, tau-b = -0.517) from BPH, through the CaP stages, to the cell lines. Thus, while nm23-H2 appears to be significant for characterizing stages of CaP, an understanding of the metastatic phenotype will require further analysis of both NM23 genes.