We have previously demonstrated that oxypurinol (40 mg/kg i.p.), a xanthine oxidase inhibitor, can reduce focal ischemic brain injury in the rat when applied pre-ischemically. By using a model of occlusion of the middle cerebral artery (MCA) in tandem with occlusion of the ipsilateral carotid artery, the present study further demonstrates that delayed (60 min) administration of oxypurinol also exhibits a protective action on ischemic damage in the stroked rat brain. Oxypurinol significantly reduced the ischemic cerebral infarct zone by preventing the development of brain damage primarily in areas distant to the central lesion core. A corresponding amelioration of brain swelling and attenuation of neurological deficits were evident. Similar protection against focal ischemic brain damage was evident when the adenosine deaminase inhibitor, deoxycoformycin (500 micrograms/kg), was administered prior to the onset of ischemia. However, with delayed (60 min) administration deoxycoformycin had no protective effect. These findings support the hypothesis that manipulation of adenosine catabolism can be an effective therapeutic approach to the prevention or treatment of brain injuries, such as those occurring during ischemic stroke or cardiac arrest.