Pelvic inflammatory disease has been inconsistently linked with ovarian cancer. We measured antibodies to Chlamydia trachomatis, to chlamydial heat shock protein (CHSP) 60, and to CHSP10, in 117 women with ovarian cancer and in 171 age- and ethnicity-matched population-based control subjects from Oahu, Hawaii. IgG antibodies to serovar D of chlamydia elementary bodies (EB) and IgG antibodies to CHSP60-1, CHSP60-2, CHSP60-3, and CHSP10 were detected using an ELISA assay. The probability of having ovarian cancer was 90% greater in women with the highest, compared with the lowest (optical density, >or =0.40 vs. <0.10), levels of chlamydia-EB antibodies (P=.05). There was also a monotonic trend (P=.09) in ovarian cancer risk associated with CHSP60-1 but not with CHSP60-2, CHSP60-3, or CHSP10. These data suggest that past or chronic persistent infection with chlamydia may be a risk factor for ovarian cancer.