OBJECTIVE The increasing prevalence of resistant strains of Neisseria gonorrhoeae has prompted investigation of new agents for the treatment of this sexually transmitted disease. OBJECTIVE This study compared the efficacy and safety of a single oral dose of enoxacin to intramuscular ceftriaxone in the treatment of uncomplicated anogenital infection with N. gonorrhoeae. METHODS A randomized open trial was conducted at a sexually transmitted diseases clinic in Brooklyn, New York. Adults with uncomplicated gonorrhea were randomly assigned to receive 400 mg of enoxacin or 250 mg of ceftriaxone. A follow-up examination was conducted 5 to 9 days later. RESULTS 59 women and 23 men were enrolled; 40 women and 19 men were evaluable. Enoxacin eradicated 18 of 19 endocervical, 10 of 10 urethral, 5 of 5 anorectal, and 3 of 3 pharyngeal gonococcal infections. Ceftriaxone eradicated 20 of 21 pharyngeal gonococcal infections. Fifty-nine pretreatment isolates of N. gonorrhoeae were available for antimicrobial susceptibility testing. The geometric mean minimal inhibitory concentration was 0.03 mg/1 for enoxacin and 0.005 mg/l for ceftriaxone. There were few sides effects in either group, and both drugs were ineffective against concomitant infection with Chlamydia trachomatis. CONCLUSIONS Oral enoxacin appears to be a safe and effective method of treatment for anogenital infections caused by N. gonorrhoeae.