Blood samples have been withdrawn simultaneously from vessels in the pulmonary circulation in 15 patients undergoing surgical resection for tumours of the lung and in 12 patients during diagnostic cardiac catheterisation procedures. A comparison has been made of the blood platelet-bound and plasma free serotonin levels in the main common pulmonary artery and pulmonary veins draining both “unaffected and affected regions” of the lung and in the brachial artery in the catheterised cases. It has been shown that platelet serotonin release may take place unrelated to changes in platelet count. The magnitude of the decrease across unaffected areas is between 3 and 30% (mean 8%) of the pulmonary arterial blood platelet-bound serotonin content. In regions of the lung involved by tumour the decrease in blood serotonin may be as much as 50% of the pulmonary arterial level (range 10–50, mean 24%). These results are from cases in which no significant platelet count changes were evident. Since the unit platelet serotonin concentration similarly decreases, the change is almost entirely accounted for by release from apparently intact platelets. Analysis of the free plasma serotonin content of the paired samples suggests that platelet serotonin release is rapidly followed by metabolism. In 5 instances large platelet losses occurred (11–90%) during transit through affected regions of the lung. Very significant decreases in whole blood serotonin content then took place. The platelet serotonin concentration in 4 of these 5 cases also decreased but in one case with 90% platelet loss, the platelet concentration increased by 50% suggesting that a rapid compensatory platelet serotonin absorption can take place in such circumstances. The comparison of the results from pulmonary and brachial artery samples taken during catheterisation were inconclusive, presumably because brachial artery sampling is too remote from the organ concerned in the serotonin release.