We determined the antimicrobial susceptibilities of 122 recent clinical isolates of Haemophilus ducreyi to 24 antimicrobial agents. All isolates produced beta-lactamase and were resistant to penicillins. The majority of strains were also resistant to tetracycline, doxycycline, and sulfamethoxazole. All isolates were susceptible to macrolides, quinolones, extended-spectrum cephalosporins, spectinomycin, rifampin, and amoxycillin-clavulanate. Reduced susceptibility to minocycline, co-trimoxazole, and kanamycin was noted. Chloramphenicol and thiamphenicol resistance was noted for the first time among southern African strains.