Some recent studies1– have emphasized the major role of serotonin (5-hydroxytryptamine [5-HT]) in the process of pulmonary vascular remodeling. An increased risk of primary pulmonary hypertension (PPH) has been reported in patients who used appetite suppressants acting on the 5-HT transporter (5-HTT). However, the mechanism by which 5-HT affects the pulmonary vasculature is still a matter of debate. Although we previously showed that 5-HTT overexpression was associated with pulmonary vascular smooth-muscle hyperplasia in patients with PPH,2– studies in relevant animal models provided evidence that not only the 5-HTT,3–4 but also several 5-HT receptors, namely 5-HT-1B,5– 5-HT-2A, and 5-HT-2B,6 may contribute to the pulmonary vascular remodeling process. However, the respective contributions of 5-HT receptors and the 5-HTT in human pulmonary hypertension (PH) have not been specifically examined. Moreover, another key issue is whether alterations in the serotonin signaling pathway may be a common pathogenic mechanism in various forms of PH.