We compared the prevalence of antibody to Chlamydia trachomatis among 88 women undergoing an evaluation for infertility and 49 women attending an antenatal clinic. Demographic data regarding sexual behavior were also collected. Eighteen women had tubal infertility and 70 had infertility due to a variety of other reasons. In comparison with women who had other causes for infertility, women with tubal infertility began coitus sooner (17.7 +/- 2.2 years vs. 19.5 +/- 3.4 years, P less than .05) and had more lifetime sex partners (4.5 vs. 1.33, P less than .001). Women with tubal infertility had a higher prevalence of antibody to C. trachomatis (13 of 18) than did women with nontubal causes for infertility (6 of 70, P less than .0001) or pregnant women (11 of 49, P = .0003). This high prevalence of antibody to C. trachomatis among women with tubal infertility was independent of sexual experience. By immunoblot analysis, an antigen of approximately 57,000 Da was immunodominant in 11 of 13 seropositive subjects with tubal infertility vs. 2 of 6 seropositive subjects with nontubal infertility (P = .046) and 1 of 11 seropositive pregnant women (P = .0003). Thus, women with tubal infertility frequently have serological evidence of prior infection with C. trachomatis and have a distinctive antigen-specific humoral immune response. These results further support the etiologic role of infection with C. trachomatis in tubal infertility.