In rats it has been shown that after adrenalectomy the toxic hypothermic response to endotoxin became intensified and blood pressure tended to decline, without reduction in pulse pressures. Terminally dyspnea appeared and arterial pressure rose, but pulse pressures became much reduced. The course was terminated by respiratory arrest. This terminal phase was characterized by an enormous rise in the right ventricular systolic pressure. The autopsy finding showed characteristic blood stagnations indicating acute right heart failure, the lung not being affected. In contrast with the case of intact rats no hemorrhagic lesions of the gastro-intestinal tract were observed. The increased susceptibility to endotoxin after adrenalectomy was completely inhibited by pretreatment with glucocorticoids or endotoxin-conditioning. The course of shock could also be checked by intravenous glucocorticoid administration during the initial hypothermic and hypotensive phase, that is perhaps of central origin. The anti-endotoxic potency of glucocorticoid was found to be almost parallel with their anti-inflammatory potency. The terminal events appeared only in the presence of intact vagi and the possibility that this terminal event may be the result of the progressive central effect has been discussed. Discussions were also made on the mechanism of endotoxin tolerance, which might differ from species to species.