Injury of the diaphragm may have clinical relevance having been reported in cases of sudden infant death syndrome or fatal asthma. However, examination of diaphragm injury after acute inspiratory loading has not been reported. The purpose of this study was to determine whether an acute inspiratory overload induces injury of the human diaphragm and to determine if diaphragm from chronic obstructive pulmonary disease (COPD) is more susceptible to injury. Eighteen patients with COPD and 11 control patients with normal pulmonary function (62 +/- 10 yr) undergoing thoracotomy or laparotomy were studied. A threshold inspiratory loading test was performed prior to surgery in a subset of seven patients with COPD and five control patients. Samples of the costal diaphragm were obtained during surgery and processed for electron microscopy analysis. Signs of sarcomere disruption were found in all diaphragm samples. The range of values of sarcomere disruption was wide (density: 2-45 abnormal areas/100 microm(2); area fractions: 1.3-17.3%), significantly higher in diaphragm from patients with COPD (p < 0.05) and with the greatest injury after inspiratory loading. We conclude that sarcomere disruption is common in the human diaphragm, is more evident in patients with COPD, and is higher after inspiratory loading, especially in the diaphragm of those with COPD.