Serotonin (5-hydroxytryptamine) (5HT) a neurotransmitter and vasoactive amine, is a major storage product of platelets that are released at sites of inflammation. Several different subtypes of serotonin receptors have been defined. 5HT receptors have been divided into three major families based on molecular, biochemical, and pharmacologic properties. Binding of serotonin to the 5HT1 family results in inhibition of adenylate cyclase whereas binding to the 5HT2 family results in stimulation of phosphatidylinositol turnover and mobilization of intracellular Ca2+. 5HT has been shown to have effects on lymphoid cells. The question of whether human T lymphocytes express receptors for 5HT and transduce signals through 5HT receptors has not been adequately addressed. As a model system, Jurkat cells (a transformed human T lymphocyte line) were examined to determine if they expressed 5HT receptors and whether 5HT stimulated an increase in inositol phosphates or affected adenylate cyclase activity. The results show that Jurkat cells bind 5HT with an average dissociation constant of 90 nM and that 5HT stimulates an increase in inositol phosphate and intracellular Ca2+ levels. These results link the 5HT receptor on Jurkat cells to the 5HT2 family; however, studies with 5HT receptor agonists and antagonists failed to clearly classify the 5HT receptor on Jurkat cells as a known member of the 5HT2 family.