1. Flight by insects is characterized by the most intense respiration known in biology and also the most controlled. Thus insect flight muscle may be the tissue of choice for the study of biochemical adaptation in the control of catabolism and biological oxidations, and many of the results obtained with insects have a significance and a relevance that transcend the boundaries between classes. In insects, such as the blowfly, flight is distinguished additionally by high wingbeat frequencies and an asynchronous type of excitation-contraction coupling. In spite of this intense muscular work, metabolic processes are not limited by the availability of oxygen. Also of importance is the morphological organization of the flight muscle and mitochondria, which have evolved ultrastructurally and biochemically into an effective catabolic machine. 2. In the fly, carbohydrate, principally glycogen, is the sole metabolic fuel; fats are not used in flight and enzymes concerned with fatty acid utilization are virtually lacking. Glycogenolysis does not lead to lactic acid; instead, the end products of glycolysis are pyruvate and alpha-glycerophosphate. The alpha-glycerophosphate cycle provides a mechanism not only for the reoxidation of glycolytically produced NADH but also for the stoicheiometric formation from each molecule of hexose equivalent of two molecules of pyruvate, which are then available for oxidation via the tricarboxylate cycle. The absence of dicarboxylate and tricarboxylate carriers from the mitochondria ensures that tricarboxylate-cycle intermediates do not exit from the mitochondrion but that pyruvate is oxidized to completion. On initiation of flight, mitochondrial oxidation of pyruvate is impeded by the lack of tricarboxylate-cycle intermediates for the generation of oxaloacetate. This is circumvented by the oxidation of proline. 3. The controls on metabolism in flight muscle, i.e. (1) glycogenolysis at phosphorylase and phosphorylase kinase, (2) glycolysis at phosphofructokinase, (3) alpha-glycerophosphate dehydrogenase, (4) proline dehydrogenase and (5) tricarboxylate cycle at isocitrate dehydrogenase, are effected by the phosphate potential and/or Ca2+. It is suggested that the metabolic changes, such as those seen in the rest-to-flight transition, are achieved by the concerted actions of these effectors at the different loci.