SummaryThis study was undertaken to determine the effect of excess phenylalanine on utilization of glucose in rat brain. 1) Carbon dioxide formation from glucose in the homogenates of fetal and adult brains was progressively inhibited as the concentration of phenylalanine was increased in the reaction mixture. On the other hand, carbon dioxide formation from pyruvate was little affected in either the fetal or adult brain when the reaction mixture was supplemented with 5 mM phenylalanine. These results indicate that the high concentration of phenylalanine does not inhibit the tricarboxylic acid cycle activity, but the glycolytic activity in the rat brain. 2) The lactate and glucose concentrations in rat brain were measured at brief intervals after the production of complete ischemia by decapitation, in order to investigate the inhibitory effect of phenylalanine on the glycolytic activity in rat brain in vivo. Lactate production during 3 minutes after decapitation was not significantly inhibited, when the phenylalanine concentration in rat brain was elevated to 0.8 to 1.0 mM.