To determine whether 'ischemic tolerance', first described in adult rodents, exists in fetal and neonatal rats, a comparison of brain injury was made between two groups of rat pups following neonatal hypoxia-ischemia (HI). One group of rat pups had previously been subjected to HI in utero (HI + HI); the other had been subjected to a sham operation (SH + HI). Brain infarct size and neuronal injury were measured 24 h after the neonatal HI insult. As indicated by 2,3,5-triphenyltetrazolium chloride staining and pathological examination, cerebral damage was significantly less in the HI+ HI group than in the SH + HI group. Induction of heat shock protein 70 (hsp70) was immunohistochemically detectable in both groups 24 h after the neonatal HI, and was proportional to the extent of tissue damage. The ischemic tolerance phenomenon observed in immature rats does not appear to be a result of induction of hsp70.