This study compared the efficacy and toxicity of 4 drug regimens containing rifampin, isoniazid, and ethambutol administered both daily and intermittently for a total duration of 6 months (26 wk). There were 411 patients with newly diagnosed, previously untreated, pulmonary tuberculosis admitted to the study. All patients received isoniazid, rifampin, and ethambutol daily in a hospital for the first 8 wk of treatment. One group continued to receive these 3 drugs daily as outpatients for an additional 18 wk; a second group received the same drugs twice weekly, and a third group received the 3 drugs once weekly during the 18-wk "continuation phase." A fourth group of patients received 2 drugs, isoniazid and rifampin, twice weekly during the continuation phase. Drug toxicity was not a major problem; drugs were permanently discontinued in only 1% of the patients. All 4 regimens were highly effective in achieving sputum negativity. By the fifty month, 100% of the patients had become culture negative. However, the relapse rate was found to be relatively high for all regimens (range, 7 to 20%). Patients with extensive disease, large cavities, heavy growth on pretreatment cultures, slow sputum conversion, persistent cavities, heavy use of alcohol, and concomitant diseases were more likely to relapse. In order to achieve relapse rates acceptable in developed countries, regimens containing rifampin and isoniazid must either be given for longer than 6 months or strengthened by the addition of supplemental drugs during the initial phase.