Histamine release by compound 48/80 was studied in vivo and in vitro in different tissues of the cat and rat. A good correlation was fond between both kinds of experiment. The histamine stores in the cat salivary gland are poorly sensitive to this histamine-liberating substance. In vitro studies with heart and lungs of the rat and guinea pig showed no correlation between the spontaneous histamine release and the release induced by compound 48/80. This finding suggests the existence of two pools of tissue histamine, both with different storage and release properties, and most probably with different functions in the body.