In adult models of ischemia and excitotoxicity, NOS+ neurons may be preferentially spared while inducible NOS (INOS)+ microglia may be upregulated. Both NOS+ neurons and microglia may then participate in ongoing cell death. In a newborn model of hypoxic-ischemic brain injury, we tested the hypotheses that neurons expressing NOS protein would survive in the selectively damaged areas of putamen and somatosensory cortex and INOS+cells would be recruited to these areas. 13, 1-2 week old piglets were subjected to 30 minutes (m) of hypoxia followed by 7m of respiratory arrest. After resuscitation, they were survived for 24 (n=4), 48 (n=4), or 96 (n=5) hours(h). 40μ sections of striatum and somatosensory cortex were processed immunocytochemically to detect the neuronal or inducible isoform of NOS. Positive cells in 8 fields in the putamen and 4 fields in the cortex were counted in 3 sections from each animal. NOS+ neurons in the putamen(#/mm2±SEM, *p<0.01)(Sham(n=5) 30.6±1.5, 24h 11.4*±6.8, 48h 6.6*±3.7, 96h 3.1*±8) were vulnerable to injury, with only a subset surviving past 24 hours. There were no differences after 24h. NOS+ neurons in the cortex, were not reduced in number after injury(Sham 4.3±0.4, 24h 4.9±0.4, 48h 1.9±0.9, 96h 3.1±1.1). INOS+ cells (#/mm2) were recruited to both areas at 96h. Cortex: Sham 118±79, 96h 950±532*, Putamen: Sham 0, 96h 360±290*. In this model, NOS+ neurons in putamen, a primary site of damage, are vulnerable to hypoxia-ischemia. The loss of the NOS protein phenotype occurs within 24h of the insult and is not progressive. In contrast, significant numbers of INOS+ cells do not appear before 96h. If neuronally derived nitric oxide is a mediator in delayed cell death following neonatal hypoxia-ischemia, only a subset of NOS+ neurons are responsible and INOS is not likely to participate in cell death prior to 96h. Supported by NINDS 20020& K081742, & AHA 95009060