Pelvic inflammatory disease (PID), one of the major sequelae of the current epidemic of sexually transmitted diseases, has been shown to be a polymicrobial infection. This study compares the efficacy and safety of two broad-spectrum combination drug regimens, cefotetan with doxycycline and cefoxitin with doxycycline, in the treatment of PID. A total of 108 patients with acute salpingitis were hospitalized and randomized into two treatment groups: cefotetan/doxycycline (N = 54) and cefoxitin/doxycycline (N = 54). Before antibiotic administration, Chlamydia trachomatis was identified in 17 (16%) of the patients, Neisseria gonorrhoeas from 72 (67%), and anaerobic and aerobic bacteria were identified from the endometrial cultures of 86 (80%). There were seven tubo-ovarian abscesses (TOAs) that were diagnosed in the cefotetan group, and six in the cefoxitin group. Clinical cure was achieved in 51 of 54 (94%) patients in each group. Of the six patients whose treatment failed, all had positive cultures for N. gonorrhoeae and facultative/anaerobic bacteria, whereas none had C. trachomatis. Two patients from each study arm whose treatment failed were diagnosed with TOAs and responded subsequently to clin-damycin plus an aminoglycoside. Cultures that were obtained after the completion of inpatient treatment showed the eradication of C. trachomatis and N. gonorrhoeae in all patients. Also, both regimens were effective in reducing aerobic and anaerobic pathogens. Finally, both regimens were well tolerated, with few side-effects.