Abstract—(1) The effects of thiamine deficiency as produced by pyrithiamine injections have been studied in the weanling mouse. Selected metabolites were measured in extracts from brain and liver of quick‐frozen animals. Pyruvate and α‐oxoglutarate dehydrogenases and transketolase were also measured.(2) In deficient brain, pyruvate and α‐oxoglutarate levels were greatly increased. Xylulose‐5‐P and 6‐P‐gluconate were more than doubled. Lactate, glucose‐6‐P, glucose and P‐creatine were moderately elevated, and ATP was increased a little. Glutamate was depressed.(3) In deficient liver, α‐oxoglutarate was much increased and ATP was twice normal. Glycogen, glucose, glucose‐6‐P, 6‐P‐gluconate, pyruvate, and glutamate were not different from the controls. Lactate was depressed.(4) Pyruvate dehydrogenase activity was reduced to 25 per cent or less in brain and liver. Transketolase and α‐oxoglutarate dehydrogenase activities were reduced to 50 per cent in both organs.(5) Thiamine treatment, within 5 hr, largely reversed the metabolite changes brought on by pyrithiamine in brain. At the same time pyruvate and α‐oxoglutarate dehydrogenase activities were increased 60 per cent or more in both brain and liver. Transketolase activity in liver was only increased 20 per cent at this time, however, and in brain was unchanged.(6) The results are interpreted to indicate that inhibition of pyruvate and α‐oxoglutarate dehydrogenases in brain is sufficient to depress in vivo function. The same seems true for the inhibition of α‐oxoglutarate dehydrogenase in liver. However, the changes seen in brain 6‐P‐gluconate and xyluIose‐5‐P probably depend on factors other than, or in addition to, the decrease in transketolase activity. It seems worthy of emphasis that in spite of the partial metabolic blocks high‐energy phosphate stores were actually increased.