The response of the sensitized guinea pig heart to perfusion, with an effective dose of ovalbumin, was found to consist of an acceleration of the rate, an increase in the amplitude of contraction, and a decrease in coronary flow, confirming the earlier observations of Wilcox and Andrus. The characteristic mechanical reaction of the isolated atria was an increase in amplitude and frequency of contraction, the more intense effects resulting in fibrillation. Electrophysiologically, atrial activity was demonstrable by bursts of action potentials, recurring as soon as the membrane had repolarized sufficiently to be re-excited. The resting potential was reduced, and the overshoot and the rate of rise of the action potential were diminished.All of the mechanical and electrical events noted in the Langendorff heart and the atrial preparations during anaphylaxis could be reproduced precisely by an appropriate dose of histamine. Evidence for the release of histamine by both the perfused heart and the isolated atria was first obtained by pharmacologic methods and then confirmed by paper chromatography of butanolic extracts.*Histamine was quantitatively estimated by a bioassay method which is discussed in detail in this report.