Cytotoxic free radicals are generated during cerebral hypoxia-ischemia and reperfusion. We studied the efficacy of allopurinol, a xanthine oxidase inhibitor and free radical scavenger, in reducing posthypoxic-ischemic damage in the developing brain of 7-d-old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was produced by ligation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before the hypoxia, the rats received either allopurinol (dose = 130-138 mg/kg) or an equal vol of saline (0.2 mL). Some pups were killed at 42 h of recovery for measurement of cerebral hemispheric water content, whereas others were killed at 30 or more d for neuropathologic examination. A total of 18 allopurinol treated rats had significantly less water content in the right hemisphere (89.07 +/- 0.32%) than 23 saline-treated animals (91.64 +/- 0.25%, mean +/- SEM, p less than 0.0001). Rank scoring of neuropathologic alterations revealed that the allopurinol treated rats were less damaged (p = 0.001). Only two of 13 brains from the allopurinol group suffered infarction compared to 10 of the 14 saline-treated animals. The results indicate that allopurinol reduces both cerebral edema and the extent of perinatal hypoxic-ischemic brain damage.