ABSTRACT.It is unclear whether placental xenobiotic metabolism can protect the human conceptus. In particular, the role of placental metabolism of toxic components of cigarette smoke such as polycyclic aromatic hydrocarbons (PAHs) is poorly understood. We hypothesized that increased aryl hydrocarbon hydroxylase (AHH) activity observed in placentas from smokers might help clear PAHs from maternal circulation and thereby prevent transplacental induction of AHH by PAHs. Our studies of AHH activity in human placentas and umbilical vein endothelium support this premise. While AHH activity was significantly increased in placentas from smokers compared with activity in placentas from nonsmokers, AHH activity in umbilical vein endothelium from these same pregnancies was unaffected by maternal smoking and remained low. In order to confirm that AHH present in endothelium was inducible, we also demonstrated dose-dependent increases in AHH activity in primary cultures of human umbilical vein endothelial cells exposed to PAHs. These findings may indicate first pass protection of the fetus by placental xenobiotic metabolism, or that endogenous factors suppress AHH induction in the fetus but not placenta.