The rate of whole body protein turnover was measured in uncontrolled diabetic patients by c15N ] glycine administration. Before insulin treatment commenced, protein synthesis and breakdown rates were within the normal range despite hyperglycaemia and a negative N-balance . Paradoxically, insulin treatment resulted in a decrease in protein synthesis and an improvement in negative N-balance. The latter was thought to result from the even larger decrease in breakdown. Whole body protein turnover was therefore investigated in the streptozotocin diabetic rat. [1 14c] J leucine was administered by constant infusion and excretion of the label was determined in expired CO2. Protein oxidation was dramatically increased by diabetes and reduced to near normal values by pre-treatment of the rats with insulin. In contrast to the protein synthesis results in diabetic patients, whole body protein synthesis in these rats we~ significantly decreased by diabetes and normalized by insulin. However, much larger decreases were observed in parallel studies on protein synthesis in individual rat tissues. Tissue protein synthesis was measured by constant infusion of [ 14c J tyrosine in control and diabetic rats. The gastrocnemius muscle showed a pronounced decline in fractional synthesis rate, but no change was detected in kidney protein synthesis rate despite a state of hypertrophy as reflected by increased protein mass . Liver protein synthesis appeared to be unaffected by diabetes, and subsequently a more appropriate method was used for measuring protein synthesis in rapidly turning over tissue like liver. Incorporation of label was measured 10 minutes after injecting a large dose of [ 3H ]phenylalanine. Protein synthesis rates were determined in liver, kidney and five muscles of control (diabetic rats treated with insulin) and diabetic (insulin withdrawn) groups. In all five muscles protein synthesis was decreased by insulin withdrawal, with the most rapid and pronounced decline being shown by the gastrocnemius. Again the kidney appeared to be unaffected. Protein breakdown rates, calculated from the changes in protein mass at the time of synthesis measurement, increased progressively in all five muscles with the duration of diabetes. With this method it was demonstrated that diabetes does reduce the overall rate of liver protein synthesis and similarly that of albumin synthesis. Total liver breakdown rates were elevated after one day of insulin withdrawal and thereafter dropped to below control values.