In an open study, a single oral dose of 400 mg of ofloxacin was administered to 40 men and 20 women who required treatment for uncomplicated gonococcal infection. Thirty-six men and 13 women were evaluable. Ofloxacin eradicated 49 of 49 urethral or endocervical gonococcal infections and 1 of 1 pharyngeal infection. There were 55 pretreatment isolates of Neisseria gonorrhoeae available for antimicrobial susceptibility testing. Twenty-four (43.6%) produced penicillinase. Eighteen (32.7%) isolates that did not produce penicillinase had penicillin MICs greater than or equal to 1.0 micrograms/mL. Twelve (21.8%) isolates had tetracycline MICs greater than or equal to 16 micrograms/mL. The geometric mean minimal inhibitory concentrations (range) for 55 pretreatment N. gonorrhoeae isolates were: ofloxacin, 0.014 (.0078-.03) micrograms/mL; penicillin, 6.30 (.125-128) micrograms/mL; and tetracycline 1.61 (.03-128) micrograms/mL. There were few side effects. Ofloxacin appears to be an effective and safe oral therapy for the treatment of infections caused by N. gonorrhoeae including infections due to penicillin- and tetracycline-resistant strains.