In 1981, 1982 and 1983, 216 multibacillary patients in Anjouan (Comores) and Burundi were treated for 8 weeks with daily rifampicin (600 mg) ethionamide (500 mg) and dapsone (100 mg) or clofazimine (100 mg) followed for 44 weeks by once weekly rifampicin (600 mg) and daily ethionamide (500 mg) and dapsone (100 mg) or clofazimine (100 mg). There were 109 previously untreated patients and 107 patients who had dapsone monotherapy, 16 of whom were infected with proven dapsone resistant Mycobacterium leprae. Clinical and bacteriological results were excellent but hepatotoxicity of this regimen remains a problem. No relapses were observed during a 2 to 6 years (mean: 4.29 years) follow-up period after the end of treatment (upper 95% confidence limit of 0.40 per 100 persons years). It is concluded that multibacillary leprosy can be successfully treated with a regimen of one year duration, but less toxic regimens, more easily applicable in the field, are necessary.