Heat-shock proteins promote cell survival under adverse environmental conditions. Synthesis of the 27-kDa (HSP27), 70-kDa (HSP70), and 90-kDa (HSP90) heat-shock proteins is increased in malignantly transformed cells and has been associated with tumor proliferation, metastasis, and resistance to chemotherapeutic agents. The increased expression of heat-shock proteins and their association with tumor-specific antigens may result in local immunity to the heat-shock proteins. We examined the occurrence of IgA antibodies to HSP27, HSP70, and HSP90 in the lower genital tracts of women with possible gynecologic cancers. Cervical samples were obtained from 119 consecutive women being evaluated for a gynecologic malignancy or returning for a follow-up examination following cancer treatment. Aliquots were tested for IgA anti-heat-shock protein antibodies by ELISA. Aliquots were also tested for IgG antibodies to HSP27 as well as for human papillomavirus. Anti-HSP27 IgA was detected in 85.7% of 21 women with endometrial cancer tested prior to diagnosis and in 41.1% of 17 women tested after treatment. In women with ovarian cancer, 77.8% of 9 women tested prior to diagnosis and 75.0% of 24 women evaluated after treatment were anti-HSP27 IgA-positive. Of 6 women with cervical cancer tested prior to diagnosis, 5 were positive for this antibody. None of 25 women with benign diagnoses or 46 healthy women were cervical IgA anti-HSP27-positive (P < 0.0001). In contrast, anti-HSP27 IgG was not associated with a gynecologic malignancy. HSP27 cervical antibodies were not associated with the presence of human papillomavirus. Cervical IgA antibodies to HSP90 were associated with ovarian cancer; antibodies to HSP70 were not cancer-associated. We conclude that cervical IgA antibodies to HSP27 may be indicators of a gynecologic malignancy. Int. J. Cancer 87:824–828, 2000. © 2000 Wiley-Liss, Inc.