The aim of the present study was to investigate the expression and distribution patterns of heme oxygenase (HO)-1 and HO-2 in human placental villi at term and in the first trimester of pregnancy using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. RT-PCR detected mRNA for HO-I and HO-2 in human placental villi during gestation. Western blotting also revealed the expression of the two distinct HO proteins throughout gestation. HO-1 was constitutively expressed, while HO-2 expression was apparently greater at term than in early pregnancy. Immunohistochemistry showed that distribution of the two HO isoforms had distinct topographic patterns: HO-1 was observed in villous trophoblastic cells, while HO-2 was found in endothelial cells and smooth muscle cells of blood vessels of placental villi. These results may provide a microtopographic basis for elucidating the mechanism of carbon monoxide (CO)-mediated vasodilatation, and it is suggested that the CO/HO system may be involved in the control of placental vascular function and may protect the syncytiotrophoblast and endothelium against oxidative injury.