We measured serum levels of anti-Gal(alpha 1-->3)Gal and anti-Gal(alpha 1-->2)Gal antibodies in 89 and 91 women, respectively, by using ELISA. These patients had cervical intraepithelial neoplasia (CIN) grades 1 to 3 and early invasive cervical carcinoma (ICC). Our objective was to compare anti-alpha-galactosyl antibody levels among them and with those of normal controls. High levels of anti-Gal(alpha 1-->2)Gal antibodies were detected in 22% of patients (P = 0.006). The mean level was 1.6 times greater than that of controls, without difference among subgroups. Thirty percent of patients had abnormally high anti-Gal levels (P = 0.001). Mean levels were twofold greater than the mean control value. Subsets with human papillomavirus/CIN 1 and CIN 2-3 had high immunoreactivity (P = 0.004). Both antibodies showed a significant correlation (r = 0.53, P < 0.00001). We conclude that 22 to 30% of patients with CIN 1-3 showed significantly high levels of anti-alpha-galactosyl antibodies. This seroreactivity might be related to the abnormal expression of alpha-galactosyl residues at some point of the natural history of human papillomavirus infection of the uterine cervix, suggesting an active immune response by natural antibodies against this virus. Further studies are needed to determine whether anti-alpha-galactosyl antibodies confer protection in human papillomavirus infection.