OBJECTIVE Our purpose was to determine whether tumor necrosis factor-alpha is produced in response to infection with Chlamydia trachomatis in the fallopian tube. METHODS Fallopian tubes were harvested at the time of abdominal hysterectomy and processed by standard tissue culture techniques. Tubal segments were inoculated with Chlamydia trachomatis serotype E/UW-5/CX. At 48 hours of incubation supernatant fluid was assayed for tumor necrosis factor-alpha. Tubal segments were stained for chlamydial inclusions and tumor necrosis factor-alpha by use of immunohistochemical techniques. RESULTS Mean tumor necrosis factor-alpha levels for infected segments were 92.1 +/- 21.3 pg/ml (mean +/- SEM) and for control segments were 61.9 +/- 13.9 pg/ml (p = 0.03 by paired t test). Tumor necrosis factor-alpha was predominantly localized in the tubal epithelium. CONCLUSIONS Tumor necrosis factor-alpha is produced in response to chlamydial infection by the human fallopian tube. It is an important proinflammatory cytokine and may promote the production of other cytokines and immune-mediated damage of the fallopian tube.