The human placenta possesses a large capacity for inactivation of prostanoids. This is due to the presence of large quantities of the NAD(+)-linked 15-hydroxy-prostaglandin dehydrogenase (PGDH type I; EC 1.1.1.141). In order to investigate whether a specific localization of PGDH is at the origin of the increasing placental PGDH activity during early pregnancy, PGDH activity was localized histochemically in placental tissue obtained in early pregnancy and at term. Intracellular PGDH activity was present in three distinct compartments in the placenta. First, the syncytiotrophoblast and second, the underlying cytotrophoblast layer of placental terminal villi contained PGDH. Third, scattered throughout the sections, we found chorion-like cells which showed strong staining for PGDH activity. The intensity of staining in samples before 12 weeks of gestation was much less than in samples after 12 weeks of gestation, which were comparable to those at term. Thus, the fetal cell layers at the boundary between the fetal tissues and the maternal blood have a great potential to inactivate prostanoids suggesting that the fetus protects itself against prostanoids of maternal origin.