The purpose of the investigation was to evaluate the effects of d-propranolol upon temporary cerebral ischemia followed by a period of reperfusion, that is, a situation analogous to major cerebral artery embolization. Twenty adult cats, lightly anesthesized with nitrous oxide, underwent 4 hours of right middle cerebral artery (MCA) occlusion and 2 hours of recirculation. Ten cats were untreated and 10 cats received d-propranolol, the weak beta-blocking isomer of racemic (d,l) propranolol. The d-propranolol was infused directly into the right carotid artery at doses of 2 mg/kg, given as a bolus immediately before MCA occlusion, and 0.33 mg/kg/hour, given continuously for 6 hours beginning immediately after MCA occlusion. Systemic arterial blood pressure was similar in both groups, but heart rate was transiently reduced in the treated group immediately after the bolus injection of d-propranolol and MCA occlusion. Regional cerebral blood flow (rCBF), measured by the xenon-133 clearance technique, was not significantly different in the ischemic, right hemisphere. Electroencephalographic (EEG) activity changes in the ischemic, right hemisphere were similar in both groups, but there was significant deterioration of EEG activity in the left, nonischemic hemisphere of untreated cats after MCA reopening. Swelling of the ischemic, right hemispheres was similar in both groups and more severe than in previous studies wherein there was no recirculation phase. Carbon perfusion and blood-brain barrier changes were also similar. The results of the study failed to show a protective effect despite theoretical beneficial actions of d-propranolol. Also, the study demonstrated that d-propranolol does not have a detrimental effect upon rCBF in acute focal cerebral ischemia.