Pelvic inflammatory disease is usually caused by Chlamydia trachomatis or Neisseria gonorrhoeae. Chlamydiae and gonococci are primary pathogens of the cervix and often ascend. Resultant damage to the cervix may permit organisms to move upward, but this mechanism of action is not well understood. Puberty and hormones, particularly oral contraceptives, may enhance chlamydial infection, but the mechanisms and likelihood of spread to the upper tract are ill defined. Upper tract infection with C trachomatis involves an acute phase, characterized by an influx of polymorphonuclear leukocytes and a chronic or persistent phase characterized by the presence of mononuclear cells (delayed hypersensitivity). Gonococci invade nonciliated epithelial cells, but are toxic to ciliated cells, due to elaborated lipooligosaccharides and peptidoglycan. Certain gonococci stimulate chemotaxis of polymorphonuclear leukocytes whose release of toxic metabolites may damage tissue. The immunologic mechanisms that permit specific host responses to these two organisms are now being elucidated and should receive more attention by researchers.