We have examined the effects of a single injection of naloxone (5 mg/kg, i.v.) in cats with cerebral ischemia produced by transorbital occlusion of the middle cerebral artery (MCA). Cerebral blood flow (CBF) was measured and the cerebral metabolic rate of oxygen consumption (CMRO2) was estimated based on measurements of arteriovenous (A-V) oxygen difference. Six cats were treated with naloxone 30 minutes after occlusion and 8 were treated 2 hours after occlusion. In 6 control animals, naloxone produced a 10-15% increase in mean arterial blood pressure (MABP), CBF and CMRO2 lasting 30 minutes. MCA occlusion reduced CBF by 70-75% in the ipsilateral MCA territory and by 15% in the contralateral hemisphere. Naloxone increased CBF by 3.5-6% in the ischemic region and 10-22% in the contralateral hemisphere in both treatment groups to the same extent as seen in control animals. There was no significant change in A-V oxygen difference and the estimated increase in CMRO2 of non-ischemic regions of both treatment groups was similar to that of control animals. These effects were transient and lasted 15-60 minutes. We have concluded that naloxone caused a transient increase in cerebral metabolism which equals or exceeds the corresponding increase in CBF. Therefore, naloxone would not be beneficial, and may be detrimental in the treatment of cerebral ischemia.