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1. Platelets and lymphocytes free of other white elements of blood have been analysed for histamine by a microchemical method. Platelets were found to contain 1280 µg. per liter or .009 µg. per 109 platelets, lymphocytes 2600 µg. per liter, or 0.6 µg. per 109 cells. 2. The histamine content of neutrophilic, eosinophilic and basophilic granulocytes has been calculated by multiple regression from histamine measurements on one series of blood samples from normal adults and another from subjects with chronic myelocytic leukemia. The normal values are 1080 µg. per l09 basophils and 160 µg. per 109 eosinophils or 2,400,000 and 360,000 µg. per liter respectively. The corresponding values for neutrophils are 3 µg. per 109 cells and 7000 µg. per liter. The values for the histamine concentration per cell are statistically significant for basophils and eosinophils, but not for neutrophils. In the leukemia series, the values for neutrophils and basophils are respectively 69 and 305 µg. per 109 cells, and they are statistically significant. The difference from normal in the value for basophils was not statistically validated. There are, however, in chronic myelocytic leukemia, histological changes from the normal that are consonant with a decreased histamine content in basophils and an increased histamine content in eosinophils and neutrophils. 3. Although definite values for the histamine content of monocytes and the immature forms seen in chronic myelocytic leukemia have not been obtained, there is reason to believe that the histamine of these cell types does not exceed that of neutrophils. 4. By centrifuging white cells in a specific gravity gradient column, partial segregation of cell types was obtained. Peak concentrations were observed at the followihig specific gravities: lymphocytic leukemia lymphocytes, 1.063; myelocytes, normal lymphocytes and basophils, all near 1.070; neutrophils, 1.080, and eosinophils, 1.080 or higher. Although individual concentration peaks were usually quite sharp, there was considerable overlapping at intermediate specific gravities. 5. About half of the histamine of normal blood is in the basophils, one-third in the eosinophils and the remaining one-sixth in all the other blood elements combined. In blood samples from patients with chronic myelocytic leukemia, the fraction of blood histamine carried by each type of granulocyte varies widely.

Enumeration of mast cells and determination of histamine in sections of dog skin and dog lung have shown that the regions of the tissue rich in mast cells are also rich in histamine. In the skin, the outer layers of the dermis contain higher concentrations of histamine and mast cells than any other region. Average values of the histamine content and mast cell count for dog liver, heart, muscle, and kidney, and for beef liver parenchyma and capsule, also exhibit a positive relationship between these two parameters, although the amount of histamine found per mast cell varied from 7 µµg. in dog skin to 32 µµg. in beef liver capsule. When the size of the mast cells was taken into account, the intracellular concentration of histamine was found to be of the same order (about 0.4 molar) for all the tissues examined except skin and kidney. In both dog skins analyzed, the intracellular concentration was about 0.1 molar. In kidney both mast cell and histamine values were too low for accurate estimation. The concentration of histamine in the mast cells investigated was much greater than the concentration in human basophils, the blood elements richest in histamine. The mechanism of the localization of histamine in mast cells is briefly considered.

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