The antibiotics that are recommended for treatment of pelvic inflammatory disease (PID) in the outpatient setting are efficacious against Neisseria gonorrhoeae and Chlamydia trachomatis. The susceptibility of non-sexually transmitted pathogens to these agents has not been well studied. The mean inhibitory concentrations of ampicillin, cefpodoxime, metronidazole, and doxycycline were determined for 137 upper-genital tract isolates from 84 women with confirmed PID. Antibiotic resistance was noted in 16%, 9%, 93%, and 72% of the facultative and 0%, 11%, 10%, and 56% of the anaerobic bacteria when tested against ampicillin, cefpodoxime, metronidazole, and doxycycline, respectively. The authors conclude that doxycycline is limited to coverage of Chlamydia and that a single dose of another antibiotic may not be adequate to eradicate the non-sexually transmitted disease pathogens from the upper-genital tract. Additional clinical and microbiologic studies are needed to determine whether the current outpatient antibiotic regimens provide optimal coverage for the non-sexually transmitted pathogens that are associated with PID.