Homeostasis of the internal environment in mammals is accomplished by a series of feedback mechanisms in a variety of tissues. Homeostasis of cell structure and function during marked changes in the environment is equally important. Both types of homeostasis are dependent on adjustments in endocrine function and changes in enzyme activity. In some instances the intracellular servomechanisms required for homeostasis match in vigor and range the perturbations of the external environment. The regulation of cell metabolism is accomplished by enzymatic, membranous and genetic mechanisms. Most peptide hormones act by combining with a specific receptor in the membrane of sensitive cells, which activates adenyl cyclase to produce cyclic AMP which in turn has selective second messenger functions. Insulin and somatotropin appear to be exceptions and may act via cyclic GMP. Steroid hormones, on the other hand, pass through the cell membrane and combine with a specific receptor protein in the cytoplasm of sensitive cells. This receptor then serves as a transport system for movement of the hormone to the nucleus where it stimulates specific protein synthesis. Nutritional effects on enzyme synthesis are partially direct and partially mediated by the endocrine system. Trace nutrients, especially the fat-soluble vitamins, appear to act directly to modify specific protein syntheses, whereas the bulkier constituents of the diet (carbohydrate, fat protein) exert their effects principally through altered rates of secretion of insulin, glucagon, and the glucocortioids. Protein-calorie malnutrition is the result of a massive assault on homeostatic and adaptive mechanisms designed to conserve nutrients and preserve life. The pathogenesis of marasmus and kwashiorkor is discussed in the light of these adaptive mechanisms.