Evidence is presented that mammals possess an inducible form of histidine decarboxylase, associated anatomically with the microcirculation, which synthesizes histamine at a rate determined by the needs of the tissues for blood under various environmental conditions. Some supporting evidence is: a) microcirculatory changes and histidine decarboxylase activation follow the same stimuli, occur at the same anatomical sites, have parallel time relationships, and are both essentially autonomous; b) histamine can reproduce all the microcirculatory changes of the slow phase of inflammation; c) the inducible enzyme has been found in every tested vascular tissue of the mouse; d) such diverse stimuli as increased room temperature, infection, and injection of reticuloendothelial system activators elicit changes in histidine decarboxylase activity consistent with microcirculatory homeostasis; e) certain poorly understood observations on the glucocorticoids, e.g., their vasoconstrictive action and the increased need for them during inflammation or infection, are compatible with the existence of a vasodilator substance, associated with small blood vessels, which may be produced at an increased rate either locally or systemically.