The activities of pyruvate dehydrogenase (PDH), α ketoglutarate dehydrogenase (KDH), and transketolase (TK) were assayed in cerebral cortex, cerebellum, pons, and midbrain regions of the rat at various stages of thiamine deficiency. Inactivation of PDH and KDH failed to precede the development of neurologic signs. While a reduction of TK activity did occur before animals become symptomatic, this ... [Show full abstract] was not significantly greater in the brain regions most sensitive to thiamine deprivation (brain stem) than in a less-sensitive region (cerebellum). None of the (3) enzymes was reduced in activity below 60% of control values even in severely deficient, symptomatic animals. It is concluded that inactivation of thiamine-dependent enzymes in rat brain does not explain the development of neurologic signs in thiamine deficiency.