Serotonin (5-hydroxytryptamine) has been known for the last half century to influence vasoactivity and to participate in neurotransmission. More recently, this compound has been recognized to cause proliferation of a variety of cells in culture, including those of vascular smooth muscle. Furthermore, the proliferative effect is synergistic with that of more conventional growth-producing polypeptides. A hypertrophic, as well as a proliferative response, has been shown to occur in some smooth muscle cells. Whether the mitogenic effect is initiated through a cell surface receptor or a serotonin transporter, or both depending on the cell type, is currently unresolved. Most evidence indicates that cellular cyclic nucleotides play an important role in the intracellular signaling process for growth regulation by serotonin, and newer studies point to protein phosphorylation pathways as being important in the mitogenic response. It has been proposed that, through these signaling pathways, serotonin plays an important role in remodeling of both the pulmonary and systemic circulations.