Chancroid is endemic in sub-Saharan Africa and enhances the sexual transmission of the human immunodeficiency virus Type 1 (HIV-1). Azithromycin is an orally absorbed macrolide antibiotic that is active against Haemophilus ducreyi, the causative agent of chancroid, and has pharmacokinetic properties that are suitable for single dosing. In a randomized single-blinded study of 127 men presenting to a referral STD clinic with culture proven chancroid, we compared the efficacy of azithromycin, administered as a single 1 g dose, with erythromycin 500 mg given 4 times daily for 7 days. Results: Cure rates were 89% (73 of 82) in the azithromycin group and 91% (41 of 45) in the erythromycin group. A failure to respond to treatment was associated with HIV-1 seropositivity and a lack of circumcision. Both regimens were well tolerated. Azithromycin, given as a single 1 g oral dose, is an effective treatment for chancroid in men, and offers major prescribing advantages over erythromycin.