Some patients with chronic airflow obstruction experience dyspnea with mild arm exercise but not with more-intense leg exercise. To investigate why these patients have limited endurance during arm exertion, we studied ventilatory responses to exercise with unsupported arms in 12 patients with chronic airflow obstruction (mean [+/- SD] forced expiratory volume in one second, 0.68 +/- 0.28 liters). Unloaded leg cycling was also studied for comparison. In the five patients who had the most severe airflow obstruction, arm exercise was limited by dyspnea after 3.3 +/- 0.7 minutes, and dyssynchronous thoracoabdominal breathing developed. In the other seven patients, arm exercise was limited by the sensation of muscle fatigue after 6.1 +/- 2.0 minutes (P less than 0.05), and dyssynchronous breathing did not occur. None of the 12 patients had dyssynchronous breathing during unloaded leg cycling. Maximal transdiaphragmatic pressure, a measure of diaphragmatic fatigue, declined similarly after arm and leg exercise in both groups. During unsupported arm work, the accessory muscles of inspiration help position the torso and arms. We hypothesize that the extra demand placed on these muscles during arm exertion leads to early fatigue, an increased load on the diaphragm, and dyssynchronous thoracoabdominal inspirations. This sequence may contribute to dyspnea and limited endurance during upper-extremity exercise.