The antimicrobial effect of sitafloxacin (DU-6859a), used either singly or in combination with rifampicin, was evaluated in vitro against Mycobacterium ulcerans. Growth of M. ulcerans was measured by plate counts and the BACTEC radiometric method. The MICs and MBCs of sitafloxacin for M. ulcerans were in the range 0.125-0.5 mg/L. The values for other fluoroquinolones were two- to four-fold higher than for sitafloxacin. Combination of sitafloxacin and rifampicin exhibited synergy with five of the eight strains, whereas the combination of ofloxacin and rifampicin resulted in additive effects only. These results suggest that the combination of sitafloxacin and rifampicin has potential in the treatment of M. ulcerans infection.