Adrenalectomized dogs maintained on desoxyeorticosterone acetate developed a fatal circulatory collapse when given normal dog plasma. They showed general restlessness, a rapid fall in blood pressure and cardiac index, a decline in central venous pressure and general prostration. Most dogs developed a bloody diarrhea and a minority showed edematous swelling of the face with itching. Animals with intact spleens exhibited marked hemoconcentration, splenectomized animals did not. Blood and plasma specific gravity determinations offered no evidence for gross plasma loss. Diphenhydramine prevented the collapse.