Summary: Chronic pulmonary disease alters skeletal muscle in humans and horses. The purpose of this study was to evaluate a possible effect of the ß2-sympathomimetic agent clenbuterol, known for its bronchodilatory and anabolic effects on skeletal musculature, on mitochondrial activity and histopathologic changes of skeletal musculature horses suffering from recurrent airway obstruction (RAO). We hypothesized that clenbuterol treatment has an effect on mitochondrial activity and histopathologic changes of RAO patients. Therefore 14 healthy horses (control) and 18 RAO patients without primary muscle disease were examined in a prospective clinical trial. In all horses a complete lung examination was performed. All horses received clenbuterol at a dosage of 0.8 µg/kg BDW bid for 2 intervals of 12 days and a 4-day-break. Muscle enzymes and muscle biopsies (M. gluteus medius) were examined histologically and histochemically at rest and 24 h after exercise before and after clenbuterol treatment. Clinical, laboratory and histopathologic examination of skeletal muscle samples excluded primary myopathies in all horses. A significant increase of mitochondrial activity was found in RAO patients compared to healthy controls. A significant reduction in mitochondrial activity was obvious after clenbuterol application in RAO patients. An effect of standardized exercise on mitochondrial activity in skeletal musculature could not be found. In conclusion clenbuterol therapy reduces skeletal muscle changes in RAO patients.