The effectiveness of rifampicin (RIF), amikacin (AMK) and their combination were estimated in the treatment of mice experimentally infected by Mycobacterium ulcerans and the risk of relapse after the treatment was evaluated. After 7 weeks of treatment with RIF or with the combination of AMK/RIF and 8 weeks with AMK alone, no viable bacilli were found in the infected tissues and these remained uninfected during the following 6 months. Among the mice treated with AMK alone, three mice relapsed, but the minimal inhibitory concentration of AMK for these isolates remained unchanged. With RIF alone, two mice relapsed and the minimal inhibitory concentration of these isolated strains was higher. However, with all the mice treated with both RIF and AMK, no relapse was observed.