The pulmonary endothelial cell removes 5-5-hydroxytryptamine (5-HT) from the circulation by a process of uptake and metabolism. The platelet, the major source of 5-HT in the circulation, represents another potential site of uptake for this amine. Platelet uptake of 5-HT infused into the pulmonary circulation was evaluated using isolated ventilated rat lungs. Lungs were perfused with buffer, platelet-poor, platelet-rich, or thrombin-treated platelet-rich plasma followed by an infusion of (14C) 5-HT. Platelet counts, aggregation response to adenosine diphosphate, and in vitro uptake of 55-HT were unchanged after circulation through the lung. In the presence of buffer or platelet-poor plasma, the lung removed 65.5 +/- 1.4% and 67.8 +/- 0.8%, respectively, of the infused (14C) 5-HT. In the presence of platelet-rich plasma, the lung removed 51.3 +/- 3.0 and platelet fraction 30.1 +/- 1.4% of the infused (14C) 5-HT. Recently aggregated platelets removed 24.4 +/- 1.8%, whereas platelets exposed to low oxyygen tensions removed 14.7+/- 0.6% of the (14C) 5-HT. These results indicate that 5-HT released inot the pulmonary circulation is either taken up by the endothelium and metabolized or taken back up by the platelet and stored.