Hypoxia increases brain adenosine concentrations, which provides neuroprotection through activation of central adenosine A1 receptors. This study was carried out to determine whether PD 81,273, which increases adenosine's binding to A1 receptors, would reduce hypoxia-induced brain injury. PD 81,273 (3 mg/kg, i.p.) decreased by about 50% the weight loss of the left cerebral hemisphere caused by hypoxia-ischemia in neonatal rats. Thus, enhancing adenosine's binding to the A1 receptor decreases hypoxic brain damage.