Thirty-six rabbits were subjected to 15-minute periods of stagnant cerebral hypoxia while blood flow to the rest of the body was preserved. After this ischemic interval the animals, divided into thee groups, received either saline, phenytoin, 15 μg/kg IV, or thiopental 10 μg/kg IV and 10 μg/kg IM. Histologic examination of tissue sections of the brains, 72 hours after ischemia, indicated that phenytoin afforded significant protection (p < 0.001) of neurons in the hippocampus and in the dentate nucleus when compared to saline, while the findings noted after thiopental were not statistically significant when compared to placebo. No statistically significant difference was noted between the two drugs. Neuron destruction was seen only in rabbits receiving either saline (92%) or thiopental (50%).