Neutralizing antibody activity to herpesvirus type 1 and type 2 was quantified in sera from 62 cases of carcinoma in situ, 137 cases of moderate to severe cervical dysplasia and 290 control women. The mean titers of antibody activity to herpesvirus type 2 were higher for carcinoma in situ cases who were less than 40 years of age than for control women of similar ages, but mean titers for older women were not different from controls of comparable ages. For women with dysplasia the mean titers of patients and controls were the same for all age groups. To evaluate the relation between type 2 antibody activity and attributes associated with an increased risk of developing cervical lesions, a II/I threshold was determined which maximally distinguished cases from controls. At this II/I threshold, 31%, 39% and 52% of dysplasia cases, carcinoma in situ cases, and invasive cancer cases, respectively, had antibodies to herpesvirus type 2 while only 28% of control women had antibodies. When examined by the method of Mantel and Haenszel, antibodies among women with neoplastic disease were significantly different from those observed in control women of comparable ages. The differences for the women with dysplasia remained after pair-matching the cases with controls by attributes of age at first intercourse, age at first marriage, age at first pregnancy, number of marriages, number of sex partners and number of live births. Although the observations do not provide proof, they are compatible with an oncogenic role of herpesvirus type 2 in neoplasia of the cervical epithelium.