We examined the effect of a 6-wk exercise training program on several skeletal enzymes in patients with chronic obstructive pulmonary disease. Eight trained their arms and 7 trained their legs. In all patients, muscle biopsy specimens were taken from the trained limbs, and in 7 patients, additional biopsy specimens were taken from the untrained limbs. The enzymes examined were citrate synthase, 3-beta-hydroxyacyl coenzyme A dehydrogenase, and pyruvate kinase. Also examined were cardiac frequency responses to incremental and endurance cycle ergometry; these responses were evaluated for arm and leg exercise, respectively. Despite the patient's increased exercise endurance, we were unable to document a significant increase in the enzyme concentrations in the trained limbs. Similarly, analyses of the cardiac frequency failed to show the evolution of the typical cardiovascular training response. This pattern is in marked contrast to that seen in normal subjects after endurance training. We conclude that patients with chronic obstructive pulmonary disease are incapable of exercising at an intensity high enough to induce the classic training response and associated changes in muscle enzymes. Therefore, other mechanisms must be important in explaining the increased endurance for submaximal exercise.