The effects of the xanthine derivative propentofylline (HWA 285), an inhibitor of adenosine transport, on ischemic brain damage have been evaluated in a model of permanent middle cerebral artery (MCA) occlusion in rats. During the postischemic survival period of 24 h, the animals were subjected to neurological and behavioral observations and then sacrificed to assess the extent of ischemic tissue damage by tetrazolium chloride. Posttreatment with propentofylline (0.01, 0.05 or 0.1 mg/kg/min, continuous i.v. infusion) initiated 15 min following MCA occlusion, produced significant reductions in infarct volumes; the highest being the most effective (reduction by 39%; P < 0.005) and improved the neurological symptoms when compared with an untreated control group. In contrast to other antiischemic agents, such as glutamate receptor antagonists, the drug induced no behavioral disturbances. This study indicates that propentofylline may provide neuroprotective effect against ischemic brain damage following stroke without negative behavioral side effects.