Plasma free and intraplatelet serotonin concentrations were measured by high-performance liquid chromatography coupled with electrochemical detection, in 30 patients with Raynaud's phenomenon of various etiologies. Serotonin was significantly higher in plasma (P less than 0.005) and in platelets (P less than 0.005) from Raynaud's patients than from normal controls. Moreover, plasma circulating serotonin could differentiate primary from secondary Raynaud's phenomenon, with significantly higher levels (P less than 0.05) for patients with an underlying connective tissue disease. Our data indicate a role for serotonin in Raynaud's phenomenon.