In an international multicentre controlled single-blind trial of 93 previously untreated lepromatous leprosy patients the therapeutic effects of adding rifampicin, 450 mg/day orally or 1,200 mg once monthly in a single oral dose, to dapsone (50 mg/day orally) for the first 6 months of treatment were compared. Clinical and histopathological improvements and bacteriological regression, indicated by the decreases in the bacterial and morphological indices of the skin and nose-blow smears, were satisfactory and practically identical after 6 months' treatment. The once-monthly rifampicin schedule was better tolerated than the daily one. In view of the good therapeutic efficacy and tolerability, the much lower cost of treatment (about one-tenth of that of the daily rifampicin regimen) and the possibility of administration under supervision, once-monthly rifampicin given in a single oral 1,200 mg dose should be recommended, along with a standard dapsone regimen, for large-scale, initial, and intensive combination treatment of patients with lepromatous and borderline-lepromatous leprosy, to help prevent an increase in dapsone resistance. A third antileprosy drug (e.g., clofazimine) may be added to this initial dual-treatment regimen.