A multicenter randomized comparative trial was done to assess the safety and efficacy of oral ofloxacin (400 mg twice daily for 10 days) versus cefoxitin (2 g intramuscularly) followed by doxycycline (100 mg twice daily orally for 10 days) for the outpatient treatment of uncomplicated pelvic inflammatory disease (PID). Neisseria gonorrhoeae (GC) grew on pretreatment endocervical cultures from 43 of 268 women (16%), and in 30 of 247 women (12%) cultures were positive for Chlamydia trachomatis (Ct). Ninety-five percent (122/128) of the women treated with the ofloxacin regimen and 93% (112/121) of those treated with the cefoxitin/doxycycline regimen had cure or improvement on examination at a minimum of one follow-up visit. All GC species were eradicated by both ofloxacin and cefoxitin. Among women who returned for follow-up, the eradication of C trachomatis was 88% (15/17) for the cefoxitin/doxycycline group and 100% (18/18) for ofloxacin. Side effects were more prevalent in the cefoxitin/doxycycline group (15%) than in the ofloxacin group (7%), nausea/vomiting being the most frequent adverse effect. In this study, it appears that ofloxacin and cefoxitin/doxycycline have similar clinical effectiveness for the outpatient treatment of uncomplicated pelvic inflammatory disease.