The effects of magnesium or zinc deficiency on growth, tissue contents of Mg or Zn and protein synthesis have been compared in 4-13-week-old rats. When maintained on Mg-deficient fodder (1.6 mmol/kg) or Zn-deficient fodder (27 mumol/kg) rats showed a reduced weight gain, whereas repletion caused increased growth rates. Pair-feeding experiments showed that this could not be attributed to reduced energy intake only. In rats maintained on Mg-deficient fodder for 14 d [3H] leucine incorporation into skeletal muscle and the heart was reduced by 24-38% compared with pair-fed controls (P less than 0.001-0.002). The incorporation of [3H]phenylalanine was reduced by 19-31%. Tissue Mg contents, however, were only reduced by 6-7% (not significant). The pair-fed rats showed no reduction in the [3H]leucine incorporation compared with ad lib.-fed animals. In rats maintained on Zn-deficient fodder for 15 d [3H]leucine incorporation into skeletal and heart muscle was reduced by 57-64% compared with pair-fed controls. The pair-fed rats showed no reduction in the [3H]leucine incorporation compared with ad lib. fed animals. In the Zn-deficient animals the content of Zn was not reduced in the skeletal muscles, whereas there was a small (15%) but significant loss of Zn in the heart. In another experiment, Zn depletion for 17 d caused a reduction in [3H]leucine incorporation of 35-41%. After 5 d of Zn repletion this defect was restored, and the [3H]leucine incorporation was above control level in the skeletal muscles. It is concluded that the intact organism is very sensitive to dietary Mg or Zn deficiency, and that the reduced growth and protein synthesis cannot easily be attributed to the reduction of tissue Mg or Zn content per se. This points to the existence of other control mechanisms mediating down-regulation of growth and protein synthesis in response to reduced dietary supplies and the ensuing drop in the plasma concentrations of Mg and Zn.