There is increasing evidence of abnormal protein metabolism in patients with chronic obstructive pulmonary disease (COPD), as reflected by lower plasma branched-chain amino acid (BCAA) concentrations and different muscle amino acid (AA) patterns than in age-matched control subjects.We examined whether the low plasma BCAA concentrations in COPD reflect an imbalance between anabolic and catabolic processes as evidenced by a low fat-free mass (FFM) and alterations in the anabolic hormone insulin and whether discrepancies in muscle AA concentrations between studies are related to different patient characteristics.AA profiles in arterial plasma and quadriceps femoris muscle and insulin concentrations in venous plasma were analyzed in 28 postabsorptive COPD patients (14 with and 14 without macroscopic emphysema) and in 28 control subjects. FFM was measured by dual-energy X-ray absorptiometry.The lower sum of plasma BCAAs in the COPD group than in the control subjects was the result of a lower leucine concentration (P: <0.001); no significant difference in valine and isoleucine was found between the groups. In the COPD group, the lower leucine concentrations were associated with low FFM (P: <0.01). Compared with the control group, the muscle-to-plasma leucine gradient was higher in the COPD group (P: <0.001) and was associated with a higher insulin concentration (P: <0.01). Several muscle AA concentrations were higher or tended to be higher in the group without emphysema than in the control group, whereas nearly all AA concentrations were lower in the group with emphysema.Leucine metabolism is altered in COPD patients and is associated with low FFM and high insulin concentrations. There were striking differences in the skeletal muscle AA profile between the COPD subtypes.