Serotonin (5-hydroxytryptamine, 5-HT) has diverse physiological functions and acts as a mitogen in a variety of cell types, including bovine placental cells. It exerts its mitogenic effect by interacting with a wide range of 5-HT receptor types. Previous studies have reported the presence of 5-HT(2) binding sites in human placental trophoblastic cells, but this has never been confirmed at the molecular level. In this study, we demonstrated that the 5-HT(2A) receptor subtype is fully expressed in the human choriocarcinoma cell lines JEG-3 and BeWo as well as in normal human placental tissue. DNA sequencing has confirmed that the 5-HT(2A) receptor present in these cell lines and tissues is identical to the human 5-HT(2A) receptor found in platelets and in the cerebral cortex. This receptor was localized by immunofluorescence on the plasma membrane, in JEG-3 and BeWo cells. Furthermore, MTT proliferation assays revealed a positive effect of 5-HT on the proliferation of JEG-3 and BeWo cells. These results suggest that 5-HT constitutes a potent mitogen for neoplastic placental cells.