I. During anaphylactic shock induced in sensitized dogs, blood was collected from the femoral and portal veins and from the supra-diaphragmatic inferior vena cava, and lymph was collected from the thoracic duct. In 8 of 13 cases of severe or fatal shock, the inferior vena-cava blood, and in 8 of 11 similar cases the thoracic-duct lymph, acquired the property of markedly stimulating the smooth muscle of the guinea-pig intestine, indicating the appearance of a physiologically active substance during shock. The corresponding inactivity of the femoral-vein blood indicates the disappearance of this substance from the blood as it circulates.[long dash]II. The active substance appearing in the inferior vena-cava blood and in the thoracic-duct lymph in dogs during anaphylactic shock is a dialyzable crystalloid of basic properties, which stimulates the smooth muscle of the guinea-pig intestine while having no effect on that of the mouse, depresses the blood pressure of the cat, and produces wkeals in human skin. The activity is associated with substances giving the Pauly reaction, as it is inactivated by condensation with diazotized sulphanilic acid. Hence, it is concluded that the active substance is histamine.