The response to short-course chemotherapy of patients with pulmonary tuberculosis caused by drug-resistant Mycobacterium tuberculosis was examined in 12 controlled trials carried out during the past decade in Africa, Hong Kong, and Singapore. Among those with initial resistance to isoniazid and/or streptomycin, failures during chemotherapy were encountered in 17% of 23 patients given a 6-month regimen of isoniazid and rifampin and in 12% of 264 patients given rifampin only in an initial 2-month intensive phase of their regimen. The proportion of failures fell as the number of drugs in the regimen and the duration of treatment with rifampin were increased, to reach 2% of 246 patients receiving 4 or 5 drugs including rifampin in 6-month regimens. The sterilization activity of the regimens, whether these included rifampin or pyrazinamide, was little influenced by initial resistance, because the sputum conversion rate at 2 months was similar to that in patients with initially sensitive bacilli, and the relapse rates after chemotherapy were only a little higher. The response in the 11 patients with initial rifampin resistance was, however, much less good, failure during chemotherapy occurring in 5 and relapse afterwards in a further 3 patients. This review demonstrates the value of rifampin in preventing failure caused by the emergence of resistance during treatment and the greater sterilizing activity of rifampin and pyrazinamide compared with that of isoniazid and streptomycin.