Acute pelvic inflammatory disease remains the major medical and economic consequence of sexuality transmitted diseases among young women. The polymicrobial origins of pelvic inflammatory disease have been well documented and the major organisms recovered from the upper genital tract in patients with pelvic inflammatory disease include Chlamydia trachomatis, Neisseria gonorrhoeae, and mixed anaerobic and aerobic bacteria. This study was undertaken to compare the efficacy and safety of cefotetan plus doxycycline with that of cefoxitin plus doxycycline in the treatment of hospitalized patients with acute pelvic inflammatory disease. A total of 68 hospitalized patients with acute pelvic inflammatory disease were entered and randomized into two treatment groups: cefotetan (n = 32) and cefoxitin (n = 36). There were six tuboovarian abscesses in each group. C. trachomatis was recovered from 7 (10%) and N. gonorrhoeae from 48 (71%) of the patients. Anaerobic an aerobic bacteria were recovered from the upper genital tract in 53 (78%) of the patients. Cefotetan plus doxycycline and cefoxitin plus doxycycline demonstrated high rates of initial clinical response in the treatment of acute pelvic inflammatory disease. Clinical cure was noted in 30 (94%) of the cefotetan plus doxycycline group and 33 (92%) of the cefoxitin plus doxycycline group. Four failures were sonographically diagnosed tuboovarian abscesses that responded to clindamycin plus gentamicin therapy. The fifth failure was an uncomplicated case that did not respond to cefoxitin and doxycycline and required additional therapy. At 1 week and 3 weeks, respectively, the posttreatment cultures demonstrated eradication, in all instances, of N. gonorrhoeae and C. trachomatis. These regimens also were very effective in eradicating anaerobic and aerobic pathogens from the endometrial cavity. Both regimens were well tolerated by the patients, and few adverse drug affects were noted.