Of 99 patients with pulmonary disease caused by multiple-drug-resistant strains of Mycobacterium tuberculosis admitted to the National Jewish Center for Immunology and Respiratory Medicine from 1983 to 1988, 29 were selected for resection to supplement chemotherapy. All patients had organisms with high levels of resistance to all of the first line medications, including rifampin and isoniazid. Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 20 of 29 were still sputum-culture-positive at the time of surgery. The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 27 of 29. Pneumonectomy was done in 15 patients; lobectomy or lobectomy plus was done in 14. Although physiologic studies before surgery indicated significant respiratory impairment in many of the patients, there were no operative deaths. There were two unrelated deaths in this series. Of the 27 survivors, 25 have remained sputum-culture-negative for a mean duration of 36 months. Compared with historical controls, resectional surgery appears to offer benefit to selected patients with pulmonary disease caused by M. tuberculosis with extensive levels of drug resistance.