Sodium/iodide symporter (NIS) gene and protein expressions have been recently described in human cytotrophoblasts, emphasizing its potential function in the active transport of iodide from the mother to the fetus. In this study we analyzed NIS expression and function in the human JAr placental choriocarcinoma cell line. Using real-time quantitative RT-PCR, we first demonstrated that NIS transcripts are expressed at a high level in JAr cells compared with other cell lines, including thyroid cancer cells. Functional analysis clearly showed that Jar cells are able to concentrate iodide in presence of hCG. Iodide accumulation increased after 2-h exposure to 5 IU/ml hCG, to 6-fold over the basal level after 8 h. This effect was reproduced using forskolin, the cAMP analog (Bu)(2)-cAMP, and phorbol acetate. Moreover, hCG increased both NIS mRNA after 2 h and NIS protein levels after 4 h, reaching a maximum after 8 h in both cases. In conclusion, our data demonstrate that 1) NIS is expressed in JAr cells; 2) iodide transport in JAr cells is regulated by hCG and by cAMP-dependent and -independent mechanisms; 3) the stimulation of iodide uptake is due to an increase in both NIS mRNA and protein levels; and 4) JAr cells may represent an excellent in vitro model suitable to analyze the molecular mechanisms involved in iodide transport from mother to fetus.