Serotonin (5-hydroxytryptamine, 5-HT) was first identified in serum in 1949 by M. Rapport.' At k that time, the importance of 5-HT was quite modest: The serum vasoconstrictor that appeared when blood was allowed to clot was an important source of artifactual vasoconstriction in investigations aimed at discovering substances possibly causing hypertension. Since then, however, a great interest has been endowed to 5-HT research, as indicated by the remarkable number of full publications in this area of research. In mammals, about 90% of 5-HT present in the body is stored in the gastrointestinal tract, mainly in enterochromaffin cells. Of the remaining 5-HT, most is present in cells of the central nervous system and circulating platelets. Part of the 5-HT that is released by enterochromaffin cells overflows to the capillary blood and reaches the liver through the portal circulation. In the liver, most of it is degraded enzymatically. Of the remaining fraction, little escapes the uptake by the pulmonary endothelium that inactivates it by means of monoamine oxidase and catechol-O-methyltransferase. The final fraction of5-HT present in the plasma is taken up avidly by platelets, which store it in their dense granules. As a consequence, as long as platelets do not aggregate, peripheral arterial blood contains little or no free 5 -HT. However, whenever platelet aggregation is initiated and dense granules release their contents, 5-HT is liberated in the blood and can exert its pathophysiological effects through activation of specific membrane receptors.