In a series of 75 patients undergoing cardiac operations with the assistance of cardiopulmonary bypass (CPB), 15 patients were subjected to relatively large hypotensive stresses during CPB as measured by the depth and duration of the fall in cerebral perfusion pressure. Of these 15 patients, eight manifested cerebral dysfunction postoperatively ranging from temporary exacerbation of pre-existing focal neurological deficits to irreversible coma. In each of these eight cases, EEG disturbances which first appeared at the time of hypotensive episodes during CPB persisted postoperatively and correlated with the nature and evolution of the clinical deficit. In two of the patients who did not regain consciousness postoperatively, neuropathological studies revealed bilateral laminar cortical necrosis, primarily involving cerebral cortex in one case and cerebellar cortex in the other, with accentuation in arterial border zones. Of seven other patients who suffered comparable exposures to hypotension during CPB, none evidenced cerebral dysfunction postoperatively. The most important determinants of this selective vulnerability to low extracorporeal perfusion pressure appeared to be the “reperfusion” pressure established after the hypotensive episode, postoperative blood pressure and cardiac output, and brain temperature at the time of the hypotension. Advanced age and history of cerebrovascular insufficiency were the greatest risk factors among patient variables.