For a better understanding of protein synthesis and degradation in the human kidney, the arteriovenous difference technique across the kidney, splanchnic organs, and leg muscle was combined with labeled leucine and phenylalanine isotope dilution models. Results indicate that in the postabsorptive state, the protein balance across the human kidney is negative because the rate of leucine release from protein degradation is greater than the amount used for protein synthesis. In the splanchnic bed, net protein balance is neutral since the amount of leucine deriving from protein degradation is similar to the amount utilized for protein synthesis. In the leg muscle, protein degradation exceeds protein synthesis. The kidney exhibits the highest leucine metabolic activity when expressed in terms of total organ leucine content. The estimated fractional protein synthesis rate in the human kidney is about 40% per day (vs. about 2% in muscle and 12% in the splanchnic bed). The human kidney presents high rates of protein turnover and accounts for a significant fraction of whole-body protein degradation, protein synthesis, and leucine oxidation.