The effects of zinc deficiency on protein synthesis and expression of specific mRNAs were assessed in rat liver. Zinc deficiency had no apparent effect on liver weight, protein content, or RNA content when these properties were compared with values obtained using pair-fed rats. However, zinc deficiency resulted in a lower rate of hepatic protein synthesis. The decreased rate of protein synthesis was due to a decrease in the rate of synthesis of proteins retained in the liver, with no apparent change in the synthesis of secreted proteins. Analysis of expression of specific gene products, as assessed by in vitro translation of total RNA followed by two-dimensional gel analysis, showed that the expression of only a few mRNAs was altered by zinc deficiency. The patterns of change in gene expression resulting from zinc deficiency varied from almost complete repression to full expression. In additional studies, cDNA clones to serum retinol-binding protein and transthyretin were used to examine the effect of zinc deficiency on the relative abundance of mRNA for these two proteins. The relative abundance of mRNA for transthyretin was specifically elevated as a result of zinc deficiency. In contrast, the relative abundance of mRNA for hepatic serum retinol-binding protein was increased in both zinc-deficient and pair-fed rats. Therefore, the observed change in mRNA for serum retinol-binding protein was apparently at least in part due to the inanition that accompanies zinc deficiency. Overall, the results suggest that zinc can regulate the synthesis of specific proteins in rat liver through changes in the relative abundance of specific mRNAs.