The cardiotoxidty of streptolysin O was first demonstrated by Bemheimer and Cantoni (1) who induced systolic contracture in the frog heart perfused with the toxin. Subsequently, Kellner et al. (2) showed that permanent and irreversible standstill, accompanied by a profound but transitory reduction in coronary flow, resulted from the exposure of the isolated hearts of guinea pigs, rabbits, and rats to small amounts of the toxin. Halpem and Rahman (3) found that the electrocardiograms of mice given large lethal doses of toxin exhibited immediate and intense bradycardia followed, in some cases, by temporary arrest; progressive atrioventricular dissociation implicated the conductile tissue. Electrocardiograms, obtained by Halbert, Bircher, and Dahle (4) from rabbits given lethal and sublethal doses of highly purified streptolysin O, were characterized by conduction defects and ventricular automatism. Intravenous injection of several multiples of the Ires0 was followed within 3-4 sec by a rapid transition from normal sinus rhythm to ventricular arrhythmia, ventricular fibrillation, and standstill. Frequently, smaller lethal doses and sublethal doses immediately produced a pronounced but transient sinus bradycardia, followed by temporary or permanent recovery. The transient nature of this bradycardia, along with the extremely rapid effects of the toxin in vivo, suggested that its toxicity might result from the release of vasoactive substances rather than from the direct action of the protein itself. Accordingly, Halbert et al. (5) studied the effectiveness of various pharmacological blocking agents in protecting against the putative physiologically active agent(s) responsible for the intravenous effects of streptolysin O. Although the several agents which exhibited protection were serotonin antagonists, there was little correlation between this property and protection. In addition, serotonin was not very toxic to rabbits and mice, so it appeared unlikely that the acute toxicity of streptolysin O could be accounted for entirely by the release of this amine.