I . Rats were fed from weaning during 3-4 weeks a high fat carbohydrate-poor diet.Control groups received a diet in which fat was completely replaced by starch in the same caloric proportion.2. The effect of this high-fat diet on the metabolism of pyruvate in diaphragm in vitro was investigated. Glycogen breakdown and glyceride content of the tissue were also measured.3. Fat diet was shown to induce a reduction in 14C0, production from labelled pyruvate and in the pyruvate uptake. Acetate oxidation was found to be unchanged after fat feeding. This gives evidence for an inhibition of the pyruvate dehydrogenase reaction in diaphragm from fatfed rats.4. The breakdown of glycogen during either an incubation in vitro or a 24-h fast was significantly reduced in diaphragm from fat-fed rats.5. Diaphragm glycerides were found to be increased four-fold by fat diet. Examination by light-microscopy of muscle sections have shown that glycerides were present in the muscle fibre and not in adipose tissue cells in the preparation.6. Inhibition of the oxidation of fatty acids by 2-bromostearate was shown t o reverse completely the impairment of pyruvate metabolism and to stimulate glycolysis. I n diaphragm from carbohydrate-fed rats 2-bromostearate induced no significant effect on carbohydrate metabolism. Similar results were obtained with glucose as substrate.7. Rats were fed the high-fat diet and then the high-carbohydrate one for a few days. This change of diet was shown to induce a rapid reversal of the inhibition of glucose oxidation in diaphragm in vitro.8. These results indicate that the impairment of carbohydrate metabolism in diaphragm from fat-fed rats is probably due to an increased oxidation of fatty acids as observed in muscle from alloxan-diabetic or starved rats rather than to enzymatic adaptations.An impairment in the metabolism of pyruvate in vivo has been demonstrated in human diabetes either by an intravenous pyruvate tolerance test [ 11 or by measuring blood-pyruvate levels during a glucose-insulin test [2,3]. It was also occasionally observed with the same methods in human obesity [4,5]. Such an impairment has been shown also in normal dog treated with lipolytic hormones or infused with free fatty acids before an intravenous glucose load [6], in alloxan-diabetic non-obese mice and in genetically obese mice by determination of expired 14C02 after injection of [14C]pyruvate to the animal [7].In vitro, the uptake and the oxidation of pyruvate have been found to be impaired in the muscle from alloxan-diabetic rats [8-