Although women bear the brunt of gonococcal infection-related morbidity, few large studies of gonorrhea treatment in women have been conducted. In a multicenter, double-blind, placebo-controlled trial, 181 evaluable women with uncomplicated gonorrhea were treated with ciprofloxacin (250 mg orally; 94 women) or ceftriaxone (250 mg intramuscularly; 87 women). Twenty-four percent of the participants were infected with antibiotic-resistant Neisseria gonorrhoeae. Cervical gonorrhea was cured in 100% (93 of 93) of the women treated with ciprofloxacin and 99% (83 of 84) receiving ceftriaxone. All pharyngeal (n = 5) or rectal (n = 20) infections treated with ciprofloxacin were cured, as were ceftriaxone-treated patients with pharyngeal (n = 6) or rectal (n = 21) infection. Geometric mean MICs (range) for 248 pretreatment isolates were: penicillin, 0.28 (0.015 to 8.0); tetracycline, 0.46 (0.06 to 4); ciprofloxacin, 0.003 (0.002 to 0.015); and ceftriaxone, 0.004 (0.001 to 0.125) μg/ml. Both drugs were well tolerated. Despite the high prevalence of antibiotic-resistant gonococci in these populations, 250 mg of oral ciprofloxacin was as effective as an injection of ceftriaxone.