OBJECTIVE Ampicillin plus sulbactam, an irreversible beta-lactamase inhibitor, was compared to cefoxitin in the treatment of women with acute pelvic inflammatory disease (PID) with and without inflammatory mass(es). METHODS Participation in an open, prospective, randomized clinical trial was offered to all women given the clinical diagnosis of acute PID who required inpatient therapy. Neisseria gonorrhoeae and Chlamydia trachomatis were sought in cervical and endometrial samples and aerobic and anaerobic species were sought in endometrial samples prior to treatment initiation. Treatment was given on at least 4 days and until women were afebrile for at least 48 h. Daily examinations were performed to assess response to therapy and safety. Only women in whom C. trachomatis was identified were discharged from the hospital on oral doxycycline to be taken for 10-14 days. RESULTS One hundred twenty-four women were evaluated for safety; 117 (94%) were evaluated for efficacy. Demographic characteristics were similar for women in each treatment group. N. gonorrhoeae was recovered from 59% and C. trachomatis was recovered from 42% of study subjects. Inflammatory masses were identified in 35/76 (46%) women given ampicillin/sulbactam and 17/41 (41%) women given cefoxitin. Ampicillin/sulbactam cured 75 ,of 76 women (98.7%) [95% confidence interval (CI) 92.9-100.0%] and cefoxitin cured 37 of,41,omen (90.2%) (95% CI 76.9-97.3%) in that treatment regimen. CONCLUSIONS Overall ampicillin/sulbactam was more effective (P = 0.05) than cefoxitin, due to superior efficacy in infection complicated by inflammatory mass(es).35/35 vs. 12/17 cured; P = 0.007).