A number of cases have been reported where, due to treatment with histamine, man and animals have shown that subsequent to such treatment they were better able to overcome the effects of histamine injected experimentally, or released in the tissues as the result of cell damage (1–15). Most of the evidence that tolerance is actually produced by such treatment is of an indirect nature. The prevention of anaphylactic shock (5, 6, 9, 10), surgical shock (8), clinical manifestations of various types of hypersensitivity (11–15), and the diminution of uterine muscle response (9, 10) to histamine have been offered as valuable support not only for the theory that the tissues are better able to withstand the release of histamine as the result of pretreatment with this substance, but also that histamine is concerned in the mechanism of these various reactions.