Background: Human papillomavirus (HPV) causes oropharyngeal and cervical cancers. Oropharyngeal cancer primarily affects whites, but cervical cancer is more common among blacks. Reasons for this distinct epidemiology are unclear. Methods: Serum was collected from women aged 35 to 60 years in the HPVin Perimenopause cohort and evaluated for antibodies to 8 HPV types. Demographic and behavioral data were collected by telephone questionnaire. Associations between sexual behaviors, race, age, HPV serostatus, and strength of serologic response to HPV were evaluated. Results: There were 781 women in this analysis, including 620 white (79%) and 161 (21%) black women. Whites were less likely to report 5+ vaginal sex partners (prevalence ratio [PR], 0.86; 95% confidence interval [CI], 0.77-0.97), but more likely to report 5+ oral sex partners (PR, 2.38; 95% CI, 1.62-3.49) compared with blacks. Seropositivity to most individual HPV types and at least 3 types was significantly lower in whites than in blacks (PR, 0.62; 95% CI, 0.47-0.80). Human papillomavirus seropositivity was independently associated with younger age among blacks, but with sexual exposures among whites. Furthermore, strength of serologic response to most HPV types significantly decreased with older age among blacks, but not among whites. Conclusions: Racial differences in immune markers of HPV exposure and the epidemiology of HPV-related cancers may be linked to differences in patterns of sexual behaviors.