Thirty-eight strains of Haemophilus ducreyi isolated in southern Africa were tested in vitro against 15 antimicrobial agents including those frequently used for the treatment of chancroid. In addition, newer compounds which possess characteristics consistent with their possible use as single-dose therapy for the disease were tested. All isolates were found to be resistant to penicillin as a result of beta-lactamase production. The majority of strains were also resistant to tetracycline, sulphamethoxazole and trimethoprim, but susceptible to co-trimoxazole, erythromycin, spectinomycin, ceftriaxone, ceftizoxime, cefodizime, ciprofloxacin, fleroxacin, rifampicin, rifabutin and FCE 22250. beta-Lactamase production appeared to be associated with the presence of low molecular weight plasmids (5.7 or 7 Md). Sulphonamide resistance appeared to be either chromosomally-mediated or due to the presence of a 4.9 Md plasmid. No evidence of plasmid-mediated tetracycline resistance was observed.