Besides neuronal transmission, serotonin (5-HT) also acts as a trophic signal during the development of the central nervous and neural crest systems. In this study, we report that in addition to trophic effect, 5-HT increases the proliferation of fetal heart cells. We showed for the first time that the cultured heart cells, express serotonin transporter (5-HTT), which confirmed the previously observed accumulation of 5-HT in developing heart. The influence of 5-HT on developing heart cells is studied throughout the dosage. We found that 5-HT concentration at physiological level, 4 microM, permits an optimal proliferation of heart cells as indicated by the number of 5-bromo-deoxyuridine immunoreactive (BrdU-im) cells and myosin heavy chain immunoreactive cells (MF20-im); fluctuation towards either concentrations reduce the proliferation. We hypothesized that 5-HTT plays a role in the heart development. Our study indicated that the blockade of 5-HT uptake by paroxetine decreased the number of BrdU-im cells and MF20-im cells. These data indicate a role of 5-HT and 5-HTT on heart development. Abnormal 5-HT level or misuse of 5-HT uptake blocker may alter the heart development.