The massive pulmonary edema caused by lethal doses of anthrax toxin in Fischer 344 rats developed only after a lag period during which signs of illness were absent. Following injection of sublethal doses of toxin, a delayed but prolonged vascular leakage in pulmonary, peritoneal, and subcutaneous vascular beds was also demonstrated. The extent of pulmonary edema was not altered nor was survival time increased by treating rats with drugs inhibiting histamine or serotonin or with drugs blocking the autonomic nervous system at several sites. A light and electron microscopic study of the lungs of rats given a lethal dose of toxin revealed that, coincident with the development of pulmonary edema, there was an elevation or detachment of the thin cytoplasmic processes of many capillary endothelial cells away from the underlying basement membrane. This structural change was followed by widespread pulmonary capillary thrombosis.