Measurements have been made of protein turnover, RNA and DNA in thymus and skeletal muscle from rats fed on a zinc-deficient diet (ZD) for 10 and 17 d, in pair-fed controls (CI) and in muscle from rats fed on the ZD diet for 24 d and then fed on restricted amounts of the deficient diet with (RIZS) or without (RIZD) Zn supplementation, for 8 d. In thymus the ZD diet induced a loss of DNA and protein which was not observed with the CI rats. Accumulation of RNA was less affected but protein synthesis was reduced. In muscle the accumulation of DNA and protein was slowed by the ZD diet, particularly in glycolytic muscles compared with oxidative muscles, and Zn supplementation increased DNA and protein. Protein synthesis and RNA concentrations were reduced in the ZD rats compared with the CI rats, but Zn supplementation at constant restricted food intake did not increase protein synthesis. Muscle protein synthesis per unit RNA varied markedly in the ZD rats after 10 d when the characteristic cycling of the food intakes and body-weight was most pronounced, the highest values being observed in the anabolic phase of the cycle although these were less than values for well-fed controls. The variability was inversely correlated with the plasma Zn levels. The extent of the variability was much less after 17 d and was not apparent in the food-restricted ZD animals. Protein degradation in muscle, assessed as the difference between overall and net protein synthesis, was faster in the ZD rats compared with the CI rats and fluctuated considerably, partly accounting for the cyclic changes in muscle after 10 d, and was entirely responsible after 17 d. The concentration of muscle-free 3-methylhistidine and its urinary excretion rate indicated inconsistent results which could not be satisfactorily interpreted. Plasma insulin was reduced in the ZD rats compared with the CI rats and was insensitive to food intake in contrast to urinary corticosterone excretion which was inversely correlated with the cyclic changes in body-weight and food intake. Furthermore, adrenalectomized rats exhibited increased mortality and reduced cycling of body-weight and food intake. Thus Zn deficiency impairs growth by a combination of reduced food intake, a reduced anabolic response to food due to a reduced capacity for protein synthesis and reduced activation of protein synthesis, possibly reflecting impaired insulin secretion, and an increased catabolic response to the reduced intake in which corticosterone may play a role.