Effects of amino acids and branched chain keto acids on leucine transamination and oxidation were assessed in peripheral human lymphocytes. Isoleucine (80–200 μmol/l) and valine (250–500 μmol/l) diminished transamination and oxidation of leucine up to 25%, glutamine (50–1000 umol/l) up to 55%. α-Ketoisocaproic acid (KIC; 200 μmol/l) augmented the activity state of branched chain keto acid dehydrogenase by 40%. It is concluded that in peripheral human lymphocytes (1) isoleucine, valine and glutamine are physiological inhibitors of leucine catabolism, and (2) leucine can promote its own degradation via KIC.