The effect of streptozotocin-induced diabetes on the turnover of acidic and basic mouse liver cytosol proteins was assessed. Previous work by others had demonstrated that acidic proteins are degraded more rapidly than basic proteins in livers of normal but not in severely diabetic animals. In this study, a milder form of diabetes was investigated to determine whether insulin-dependent diabetes in the absence of starvation, large weight losses, and impending death results in fundamental changes in degradation of the normally labile (acidic) proteins and stable (basic) proteins. The relative rates of degradation of liver proteins were measured by a double-isotope technique and by the loss of protein radiolabeled with [14C]-bi-carbonate. The relative rates of synthesis of proteins were estimated by incorporations of [3H]-leucine. No fundamental change in the relative rates of synthesis or degradation of acidic and basic proteins was observed. There was a general decrease in the incorporation of radiolabeled amino acids in the diabetic state and an increase in the specific activity of some amino acid–metabolizing enzymes, indicating changes in amino acid metabolism in liver. A study of the quantity and subcellular distribution of several liver cell proteinases revealed little if any changes in the proteolytic machinery of liver cells in this form of insulin-dependent diabetes. Thus, the fundamental changes in protein degradation seen in severe diabetes are not observed in a less severe form of the disease.