The effect of a deficiency of calories and/or nitrogen on protein metabolism in the rat was investigated. During the 5 days of the study, the rats received all nutrients except water via intravenous hyperalimentation. Four diets were used: I) 1.25 g amino acids, 12.5 g glucose/day; II) 1.25 g amino acids/day; III) 1.25 g glucose/day; and IV) 12.5 glucose/day. The rate of protein synthesis in heart, lung, muscle, kidney, and liver was estimated by a modification of the technique of Garlick et al. (The diurnal response of muscles and liver protein synthesis in vivo in meal-fed rats. Biochem. J. 136: 935-945, 1973) except that [15N]glycine was used as the tracer. Heart and lung protein synthesis was depressed by both caloric and nitrogen restriction. Muscle protein synthesis was only significantly affected by omission of calories from the diet. Kidney nitrogen content increased with the amino acid diets and decreased with the nitrogen-deficient diets. The major response of the liver to a dietary deficiency was to lose nitrogen via an increase in the rate of liver protein catabolism.