Since sulphonamides are no longer predictably effective in the treatment of chancroid the combination of trimethoprim-sulphamethoxazole (TMP-SMX) was evaluated to identify other effective regimens. One hundred and nine patients with genital ulcers (75 men and 34 women) seen at the Special Treatment Clinic in Nairobi, Kenya, were randomly assigned to treatment with a seven day course of either sulphamethoxazole 1000 mg twice daily or trimethoprim (160 mg)-sulphamethoxazole (800 mg) (TMP-SMX) twice daily. Haemophilus ducreyi was isolated from the ulcer in 57 patients (33 men and 24 women). 16 patients were subsequently diagnosed serologically as having syphilis. No aetiological diagnosis was made in 40 patients. Treatment with sulphamethoxazole failed in five of 21 (24%) culture positive patients who were available for evaluation after seven days, whereas all 19 of such patients who were treated with TMP-SMX responded to treatment. Of the 21 isolates available for susceptibility testing, all were susceptible to trimethoprim alone (MIC less than 0.5 mg/l) and three were resistant to sulphonamides, all three containing a 4.9 megadalton (Mdal) plasmid. Two of the three patients from whom these isolates had been obtained were treated with sulphamethoxazole and both were clinical and bacteriological failures. Five of six patients with sulphonamide-susceptible H ducreyi responded to treatment with sulphamethoxazole. Failure of sulphonamides to eradicate H ducreyi in some patients with chancroid is associated with the presence of a sulphonamide resistant plasmid. In regions where this plasmid is present in H ducreyi TMP-SMX is the preferred treatment for chancroid.