The dependency of a high level of serotonin (5-hydroxytryptamine, 5HT) in the lung on blood 5HT was examined. The whole lung excised from NOD/Shi mice (male, 8-12 week old) immediately after being sacrificed by cervical dislocation contained 2.86 +/- 1.21 micrograms/g of 5HT per wet tissue. This amount was much higher than that explained by the included blood which was estimated by the hemoglobin concentration in the lung extract. In order to decrease 5HT level in the blood, platelet was depleted by an exposure to gamma-ray. On the 10th day after the irradiation the amount of 5HT in the lung and blood decreased to about 3.1% and 1.5% of the respective normal values. The progressive decrease in 5HT in the lung and blood of the irradiated mice was prevented by the transplantation of normal bone marrow cells (10(7) cells/mouse). 5HT in the intestine did not change significantly. The correlation between 5HT in the excised lung and the number of platelets in the blood was statistically significant (correlation coefficient r = 0.61). The irradiated, platelet-deficient mice were incapable of accumulating serotonin in the lung, while normal mice increased the lung serotonin more than 3-fold, when high doses of 5HT were administered. The results indicated that the high level of 5HT in the dissected lung was closely related to platelet in the blood. A question remained where the majority of the measured 5HT was located in the lung tissue.