We determined the susceptibilities of 94 strains of Haemophilus ducreyi isolated in various municipalities in the United States between 1982 and 1989 to the following antimicrobial agents: amoxicillin-clavulanic acid, ceftriaxone, erythromycin, azithromycin, ciprofloxacin, ofloxacin, trimethoprim, and spectinomycin. Ceftriaxone (MIC, .0.008 ,g/ml), azithromycin (MIC, <0.125 ,Lg/ml), erythromycin (MIC, .0.125 ,ug/ml), ciprofloxacin (MIC, <0.25 ,ug/ml), and ofloxacin (MIC, .0.25 ,ug/ml) were highly active against all isolates. Amoxicillin-clavulanic acid (MICs, 0.25 to 8.0 ,ug/ml), trimethoprim (MICs, 0.06 to 16.0 ,ug/ml), and spectinomycin (MICs, 2.0 to .32.0 jLg/ml) were less active against these isolates. Isolates possessing the 5.7-MDa 1-lactamase plasmid were less susceptible to erythromycin, trimethoprim, and spectinomycin than were isolates possessing the 3.2-MDa I5-lactamase plasmid. The susceptibilities of plasmidless isolates to erythromycin, trimethoprim, and spectinomycin were distributed bimodally; the median MIC for the more susceptible plasmidless isolates corresponded to that for isolates with the 3.2-MDa plasmid, and the median MIC for the less susceptible plasmidless isolates corresponded to that for isolates with the 5.7-MDa plasmid. Thus, plasmid profiles may be valuable markers for geographical variations in antimicrobial susceptibilities of H. ducreyi strains that may indicate the relative efficacy of regimens for the treatment of chancroid. Of the regimens recommended by the U.S. Public Health Service for the treatment of chancroid, our results support the use of erythromycin, ceftriaxone, and ciprofloxacin, and perhaps ofloxacin, but suggest that amoxicillinclavulanic acid and sulfamethoxazole-trimethoprim should be used with caution.