Relationship between the prevalence of the antibodies to HPV16E7 and L2 proteins and the development of cervical cancer was examined. Sera from 57 patients with invasive cervical cancer and from 200 age-matched healthy blood donors (16 to 64 years old) were examined for antibodies against E7 and L2 proteins of human papillomavirus (HPV) type 16. Bacterially expressed fusion antigens were used in a Western immunoblot assay. Ten (18%) of the patients and 10 (5%) of the controls were positive for only E7. Each eighteen of the patients (32%) and of the controls (9%) were positive for only L2. Three of the patients and 2 of the controls were positive for both E7 and L2 antibody reactivity. The patients' prevalence of antibodies for the E7 and L2 proteins was significantly higher than that of the controls (E7: x 2 =14.3, p <0.01; L2: x 2 = 23.8, p <0.01). On the other hand, neither sex specific difference in the antibody prevalence was observed, nor was there any difference in the antibody prevalence with age. Our findings indicate that antibodies to the HPV16L2 proteins could be a parameter for cervical cancer development as well as those to the HPV16E7 proteins. human papillomavirus; type 16; serum antibody; L2 protein; E7 protein Human papillomaviruses (HPVs) are a heterogeneous family of DNA viruses that are associated with a variety of epithelial lesions. The viruses are classified into types by genotyping, i.e., types are all defined as isolates that display at least 50% DNA homology in a liquid hybridization assay (Coggins and zur Hausen 1979). HPV type 16 is associated most frequently with malignant proliferative lesions, including uterine cervical cancer (zur Hausen and Schneider 1987).Diagnosis of viral infection is generally based on the detection of serum antibodies that react with virus antigens. However, the efforts to detect specific