The effect of an ultra-short acting barbiturate, methohexital, on the distribution of blood flow in baboon cerebral cortex was studied following occlusion of the middle cerebral artery under conditions of constant blood pressure. Further experiments assessed the effects of methohexital and pentobarbital on the threshold relationships (established in earlier work) between flow, cortical evoked potential amplitude and extracellular potassium activity. Regional flow was measured by the hydrogen clearance technique and the initial anesthetic was chloralose in all experiments. If flow after occlusion was >25 ml/100g/min, so that electrical activity was sustained, methohexital reduced flow in proportion to the flow (r = -0.84, p< 0.001), but if flow was <20 ml/100g/min, and electrical activity was reduced or absent, a significant elevation in flow occurred averaging 3.4 ml/100g/min (p<0.01), an appreciable fraction of ambient flow. This result may be attributable to an inverse steal, blood being diverted into ischemic regions from vasoconstriction Induced in relatively well-perfused areas. No statistically significant change could be demonstrated either in the flow threshold for the abolition of the evoked potential or in that for the massive increase in potassium, although methohexital tended to decrease, and pentobarbital to increase, these thresholds. However, methohexital significantly reduced the rate of decrease of the evoked potential for a given flow below the threshold. These effects may be among factors underlying any protective effect of barbiturate in focal cerebral ischemia on the neurological and neuropathological levels. © 1979 American Heart Association, Inc.