We describe two cases of pulmonary infection due to Mycobacterium xenopi (M. xenopi). Both cases were men, ages 61 and 54 yr. In the first patient, lung infection due to M. xenopi occurred after gastrectomy. The second patient had an inactive M. tuberculosis infection. Both had pulmonary symptoms including cough, sputum and fever. Each chest X-ray showed an infiltrative shadow with a cavity in a unilateral, upper lobe. Isolates from both patients were studied not only by microbiological characteristics but also by DNA-DNA hybridization. All isolates were susceptible to streptomycin and kanamycin. In the first case, the patient had initially received rifampicin, isoniazid and ethambutol despite in vitro susceptibility patterns, however, there was no response and a new infiltrative shadow appeared in the contralateral lobe. With a multiple drug regimen based on in vitro susceptibility, clinical and roentgenographic improvements were achieved. The second patient showed a favorable response to the initial chemotherapy. Pulmonary infection due to M. xenopi can generally be successfully treated with drugs to which the organisms show in vitro sensitivity. We also reviewed the other two cases reported in Japan.