The incidence of cervical cancer increases with age among USA Hispanics and women living in Latin America starting in the fourth decade of life. We conducted a study of women > or = 40 living at the USA-Mexico border to determine the prevalence and risk factors for human papillomavirus (HPV) infection detected by polymerase chain reaction. In all, 9.2% of participants tested HPV positive. Compared with women aged 50-59, odds ratios of 8.82 and 6.67 were observed for women > or = 60 and 40-49, respectively. Among women aged 40-49, both oncogenic and non-oncogenic HPV infections were detected; however, women > or = 60 were positive for predominantly oncogenic genotypes. HPV risk significantly increased with > or = 2 lifetime sexual partners in adjusted models. These data suggest that the prevalence of HPV infection may have a second peak among post-menopausal Hispanic women.