Twenty-two patients undergoing thoracotomy for the diagnosis or treatment of a suspected pulmonary neoplasm had separate biopsies taken from their external and internal intercostal muscles at the time of surgery. Pulmonary function abnormalities ranged from none to moderate airway obstruction. Seventeen of the twenty-two patients had morphologic changes (targeting, variation in fiber size, splitting, and atrophy) in both respiratory muscles, but not in the control latissimus dorsi. Fiber atrophy was more marked in the internal intercostal muscle and was significantly related to the degree of airway obstruction, but not to age, malignancy, or weight loss. Biochemical analyses revealed decreased adenosine triphosphate (ATP) and phosphocreatine (PC) in 47 of 52 muscles, including the latissimus dorsi. The data suggested a relation between increasing airway obstruction and decreasing amounts of phosphocreatine in both intercostal muscles. This relationship may have been enhanced by the presence of malignancy or weight loss. There was a selective decrease in muscle glycogen found only in the external intercostal muscle that was not affected by airway obstruction, malignancy, or weight loss. Intercostal muscle abnormalities are common in patients with obstructive lung disease who undergo thoracotomy, and are probably multifactorial in origin. It is possible that these abnormalities affect the natural history of lung disease in some patients.