The involvement of the nm23 gene, initially documented as a putative metastasis-suppressor gene, in normal development and differentiation has been supported by several investigations. To date, however, localization and expression pattern of nm23 in the human placenta has not been determined. In the present study, the expression of nm23-H1 was examined by Northern blot and immunohistochemical analyses in human placentas from various stages of gestation. In first trimester placenta, the villous cytotrophoblast and the extravillous trophoblast exhibited strong cytoplasmic staining for nm23-H1. In second trimester and term placentas, the few cytotrophoblasts present showed less intense staining than those in first trimester placenta. Northern blot analysis demonstrated a progressive decrease in nm23-H1 gene expression with advancing gestational age, which is consistent with the results obtained by immunohistochemistry. These findings suggest that nm23-H1 is involved in the differentiation process of the trophoblast, and high levels of nm23-H1 expression seem to reflect the proliferating, less differentiated state of that reserve.