This study sought to determine risk factors for genital infection with papillomavirus (HPV) in Panamanian women 20-49 years old. Subjects were randomly selected from Herrera and Panama provinces (cervical cancer incidence 79 and 25/100,000, respectively). Participants were interviewed to determine sexual behavior. Cervicovaginal lavage specimens were obtained to test for HPV DNA by commercial dot blot hybridization. HPV-16/18 DNA was detected significantly more frequently (5%) in Panama than Herrera (2%) samples (P = .002). Clearly, infection with high-risk HPV types alone cannot account for the differences in cervical cancer incidence between the two populations. HPV-16/18 detection decreased with increasing years of sexual experience among all women in Panama and among women with multiple partners in Herrera. However, HPV-16/18 detection did not change with sexual experience among monogamous women in Herrera. Thus, the epidemiology of HPV is complex and reflects both virus- and population-specific factors.