To investigate the role of retinoids on human placental development and functions, we characterized the spatial distribution of retinoid receptors in human term chorionic villi. In situ hybridization with 35S labeled sense and antisense probes for the RARs, α, β, γ and RXRs, α, β, γ, specifically detected only RARα and RXRα. Both RARα and RXRα mRNA were preferentially expressed in the trophoblast cell layer. This syncytiotrophoblast expression was confirmed by immunohistochemical analyses using anti-RARα and RXRα antibodies. Using trophoblast cells in culture, we then studied the effect on hCG secretion of 0.1μ M RA physiological forms and of selective RARα and RXRα synthetic agonists. Only RXRα specific ligands such as physiological 9-cis RA and synthetic Ro 25-7386 stimulated hCG secretion (doubled). These results suggest an important role for RXRα in human placental development and function.