In a study in Singapore, Chinese, Malay, and Indian patients with sputum-smear-positive pulmonary tuberculosis were allocated at random to daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide for 2 months (2SHRZ), 1 month (1SHRZ), or 2 months without streptomycin (2HRZ), followed, for all patients, by 3-times-weekly isoniazid and rifampin (H3R3) up to 6 months. At 2 months, the culture-negativity rate for the 2SHRZ series was statistically significantly higher than for either of the other 2 series. All 319 patients with drug-sensitive tubercle bacilli pretreatment had a favorable bacteriologic response during chemotherapy except for one 2SHRZ/H3R3 patient, and among the 300 patients assessed during 24 months of follow-up after chemotherapy there was only 1 bacteriologic relapse in each series, giving an overall therapeutic failure rate of only 1%. Thus, the 2SHRZ combination had the highest early sterilizing activity, but the potent continuation therapy compensated for the initial inferiority of the other 2 regimens. Among the 32 patients with tubercle bacilli resistant pretreatment to isoniazid, streptomycin, or both drugs, there were no failures during chemotherapy and 3 subsequent relapses among the 30 assessed during 24 months of follow-up. Eleven (3%) of the 420 patients who started chemotherapy on their allocated regimen had hepatitis with jaundice during chemotherapy. However, 2 of these had cirrhosis pretreatment and 1 was a chronic alcoholic.