Between August 1983 and October 1990, 42 patients with resistant Mycobacterium tuberculosis underwent 44 pulmonary resections. During the same time, 38 patients with mycobacterial infections other than tuberculosis had 41 pulmonary resections. All patients either were poor candidates for medical therapy alone or had existing complications requiring surgical intervention. There was one operative death in each group, both from adult respiratory distress syndrome (postpneumonectomy pulmonary edema). Complications were high, with bronchopleural fistula most commonly occurring after right pneumonectomy in patients infected with Mycobacterium avium with superimposed infection with nonmycobacterial pathogens. In patients undergoing pneumonectomy for resistant Mycobacterium tuberculosis, the left lung was most often resected. It is recommended that if localized disease is present and medical treatment is likely to fail, pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection after 3 months of drug-specific therapy. Muscle flaps were used frequently to avoid residual space and bronchial stump problems. Earlier resection in patients with indolent nontuberculous mycobacterial pulmonary infections is advocated before extensive polymicrobial contamination and right lung destruction.