Chemotherapy of pulmonary disease due to Mycobacterium kansaii has not always been successful, and resectional surgery has been used frequently in the treatment of this infection. To ascertain the impact of new antimicrobial agents on the treatment of M. kansaii infection, we reviewed the clinical courses of 59 patients treated between 1971 and 1974. Over-all, 92 per cent of patients converted their sputum cultures while receiving drugs, with only one patient undergoing surgical resection. Regimens containing rifampin were universally effective in both initial and retreatment cases; however, they offered no significant advantage over monrifampin regimens in initial treatment cases. In vitro resistance to isoniazid and ethambutol did not adversely affect the results of treatment with these drugs. Owing to the effectiveness of current chemotherapy, parameters such as age, underlying lung disease, or extent of disease were not related to the outcome of therapy. Because 90 per cent of the conversions in successful regimens occur within 4 to 6 months of beginning therapy, patients whose cultures remain positive should be considered for alternate drugs. Because the frequency of relapse after current chemotherapy is not yet clear, and because rifampin appears to be particularly advantageous in retreatment programs, rifampin should be reserved for this role. The total course of treatment should probably span at least 18 months, or 6 months beyond any cultural or radiographic evidence of activity.