The adenosine A1 binding enhancer PD 81,273 provided significant neuroprotection against hypoxic-ischemic brain injury in newborn rats. Because PD 81,273 selectively potentiates ADO A1 receptor activation in hypoxic tissues, this protective agent may produce fewer side effects than those seen with ADO A 1 receptor agonists and nonselective ADO receptor potentiating agents. 