We tested 383 women with and 500 women without cervical neoplasia for antibodies against Chlamydia trachomatis or herpes simplex virus (HSV). Exposure to both agents was related to sexual activity, with the highest prevalence of antibodies found in women with more sex partners and who had first coitus at an earlier age. When subjects were matched for several risk factors (age, race, marital status, parity, number of sex partners, and history of venereal disease), a significant excess of antibodies against C trachomatis was found in cases as compared with control subjects (76.5% v 58.4%, respectively; n = 149). Because matched-pair analysis lost a substantial proportion of women with neoplasia (largely because they were older), linear logistic analysis was performed. This also showed an excess of antichlamydial antibody in cases, with an estimated odds ratio of approximately 2 for the association of antichlamydial antibody and the risk of being a case. Neither analysis found an excess of antibodies to HSV type 2 in cases.