Two therapeutic regimens of one-year duration were administered to two groups of 20 previously untreated multibacillary leprosy patients. Regimen A was rifampin 600 mg twice weekly, prothionamide 500 mg, and dapsone (DDS) 100 mg daily for six months, followed by 100 mg DDS daily for another six months. Regimen B was identical to Regimen A but without prothionamide. Follow-up was for 4 1/2 and 5 years in 15 and 14 patients, respectively. Clinical improvement was rapid, and the bacterial index (BI) of the patients diminished by one unit per year after stopping treatment. Five patients were skin-smear negative at 54 months. The BI in the nasal mucosa became negative after 48 months. There were many attacks of erythema nodosum leprosum between month 3 of treatment until 13 and 21 months. Up to now no relapses have been observed. These results have confidence limits of 20% and 23%, respectively. However, when the results of the two regimens are added, the confidence limit for six months' twice weekly rifampin together with DDS and followed by six months of DDS and 4 1/2 years follow-up is 12%.