Eighteen patients with severe COPD and seven healthy control subjects 64.0 +/- 2.2 and 66.8 +/- 1.4 yr of age, respectively (mean +/- SEM), were investigated. Arterial blood gas analysis, dynamic lung volumes, and muscle biopsy specimens from the quadriceps femoris muscle were performed. The muscle biopsies were analyzed for citrate synthase (CS), succinic acid dehydrogenase (SDH), 3-hydroxyacyl-CoA dehydrogenase (HAD), phosphofructokinase (PFK), and lactate dehydrogenase (LDH) activities and related to protein content. The PFK activity was higher in the COPD group than in the control group (+34%, p < 0.05). CS showed a group difference in the opposite direction (-29%, p < 0.05). LDH activity followed PFK and tended to be higher in the patient group (+27%, NS), whereas SDH (-31%, NS) and HAD (-28%, NS) mirrored the CS results. Muscle protein concentration tended to be lower in the COPD group (-14%, NS). There were no significant changes in enzyme activity after 7 mo of long-term oxygen therapy (n = 6). These results indicate adaptation in the form of augmented glycolysis (PFK), and decreased aerobic metabolism (CS) in the quadriceps femoris muscle in patients with advanced COPD.