The efficacy of single dose enoxacin, 400 mg was compared to ceftriaxone, 250 mg IM for therapy of uncomplicated gonorrhea in 152 evaluable patients attending sexually transmitted disease clinics in Baltimore, Indianapolis and Seattle. Anogenital gonorrhea was cured in 75 (99%) of 76 patients treated with enoxacin and 73 (97%) of 75 patients treated with ceftriaxone. Three of three patients with pharyngeal gonorrhea were not cured by enoxacin while all three ceftriaxone treated cases of pharyngeal gonorrhea were cured. All cases of anogenital gonorrhea caused by beta-lactamase producing Neisseria gonorrheae (11 patients), gonococci with high-level, plasmid-mediated tetracycline resistance (11 patients), or gonococci with chromosomally mediated penicillin resistance (22 patients) were cured. The IC90 for enoxacin of N. gonorrhoeae isolated in this study was 0.06 microgram/ml. Enoxacin appears to be a well tolerated, efficacious alternative to currently recommended therapy for patients with uncomplicated, anogenital gonorrhea including cases potentially caused by antibiotic resistant N. gonorrhoeae.