The metabolic adaptation in man to starvation, semistarvation, and carbohydrate restriction is complex and involves a number of hormones, substrates, and tissues. In particular, however, the need for the ketoacids beta-hydroxybutyric acid and acetoacetic acid to replace glucose as the primary fuel for the brain of fasting man appears to be the key to maximum protein conservation. That is, ketogenesis is necessary to provide the brain with a fat-derived, water-soluble, insulin-independent, glucose-equivalent fuel. This adaptation is associated with a small loss of the ketoacids into the urine (100-150 mM/day or 40-60 calories/day). The ketonuria, in turn, necessitates increased renal utilization of muscle-derived glutamine. Synthesis of glutamine by muscle requires muscle proteolysis. Administration of glucose in amounts needed to meet the requirements of the brain results in suppression of ketogenesis in fasting man and a significant diminution in nitrogen mobilization and utilization as well.