Vulnerability of neurotransmitter-specific neurons to hypoxia-ischemia was examined in the immature rat corpus striatum. Carotid artery ligation plus 2 hours of 8% oxygen atmosphere at 1 week of age produced ipsilateral striatal injury and reduced hemisphere mass 2 and 6 weeks later. Striatal injury was always more severe than damage to overlying cortex. Over half the animals had status marmoratus, a neuropathological change seen in the basal ganglia and thalamus after hypoxic-ischemic injury in full-term human infants. Two weeks after the insult, markers for cholinergic, dopaminergic, and gamma-aminobutyric acid-containing neurons were all reduced, but the reduction in cholinergic markers was greater than that for the other two transmitters. Muscarinic cholinergic receptors were relatively preserved, but their distribution was disrupted. In adult animals specific activity of cholinergic neuronal markers was normal, suggesting that the balance of neurotransmitters was restored after the early insult.