Forty patients with pulmonary disease caused by Mycobacterium kansasii were treated initially with rifampin, isoniazid, and ethambutol daily for 12 months, and with streptomycin twice weekly for the first 3 months. Postchemotherapy follow-up examinations have ranged from 6 to 68 months, with an average of 31 months. One of the 40 patients (2.5%) relapsed 6 months after completion of chemotherapy. In vitro susceptibility of the mycobacteria to the drugs used, extent of disease, and/or the coexistence of other diseases did not seem to influence the outcome. This 12-month chemotherapy regimen is considered to be sufficient for the initial treatment of pulmonary disease caused by M. kansasii.