Placental growth has several malignant characteristics, including properties of invasiveness, rapid cell proliferation, and a lack of cell contact inhibition. These malignant characteristics of placental development are strictly regulated throughout normal gestation, because placental growth is limited in both extent and duration. Transforming growth factor-beta-1 inhibits growth of many normal and malignant cell lines. In this study, using Northern blot analysis, we found transforming growth factor-beta-1 expression to occur in human placenta throughout gestation. Peak expression was noted at midgestation (near 17 weeks) and again in late gestation (near 34 weeks). Immunohistochemical analysis localized transforming growth factor-beta-1 protein expression to the syncytiotrophoblastic layer. The process of trophoblastic invasion of the decidua and myometrium is usually complete by 18 weeks of gestation, and absolute growth of the placenta ceases in late gestation (near 35 weeks). The time frames of maximal transforming growth factor-beta-1 expression noted in our studies correlate with these events. We speculate that peak transforming growth factor-beta-1 expression at these stages of placental development is suggestive of its regulation of both trophoblastic invasion and proliferation.