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The neurotoxic lesion produced by direct injection of 25 nmol ofN-methyl-d-aspartate (NMDA) into the corpus striatum of 7-day-old rats was compared to the effects of injecting 75 nmol into the striatum or hippocampus of adults. The area of histopathology in the immature striatum was 21 × larger than the striatal lesions in adults. Damage from NMDA injected into the immature striatum also extended into the dorsal hippocampus and produced an area of destruction which was 16 × larger than observed after direct injection into the adult hippocampus. Several studies have implicated excessiveN-methyl-d-aspartate receptor activation in the pathogenesis of hypopoxic-ischemic and hypoglycemic injury and our results suggest that this neurotoxic mechanism is extremely active in the immature brain.