Fleroxacin was prescribed to treat both HIV-negative and HIV-positive men with proven chancroid in an open study. HIV-negative men were treated with a single 400-mg dose of fleroxacin, and HIV-positive men were treated with 400 mg daily for 5 days. Three of the 58 evaluable HIV-negative men were clinical and microbiologic failures, and two of the 22 evaluable HIV-positive men had persisting infection with Haemophilus ducreyi. Both regimens were well tolerated. Fleroxacin is an acceptable alternative to existing treatment regimens for chancroid in men.