The purpose of this investigation was to study the occurrence of human papillomavirus (HPV) infection in relation to the interval between menarche and first intercourse. Two hundred eight subjects, aged 13 to 21 years, were recruited from an ambulatory adolescent clinic. Patients were excluded if they had a history of genital warts or an abnormal Papanicolaou smear. All subjects completed a self-administered questionnaire regarding demographics and their menstrual, sexual, and contraceptive histories. HPV infection was determined by in situ hybridization or changes consistent with HPV on a Papanicolaou smear, or both. The prevalence of HPV infection was 19.2%. The average interval between menarche and onset of sexual activity was 26.6 months for those who were found to have HPV infection compared with 35.7 months for those whose test results were negative (p = 0.02). First sexual intercourse within 18 months of menarche was associated with a significant elevation of risk of HPV infection, in comparison with that in adolescents who postpone first intercourse 3 to 4 years after menarche. These data suggest that factors such as increased biologic vulnerability may play a role in HPV infections among adolescent women.