Background: This study examined the acceptability of preventive human papillomavirus (HPV) vaccination among Latina immigrants and African American women through eight focus groups (n = 55, 28 Latinas and 27 African Americans). Methods: Latinas were between 17 and 39 years old (x = 27.9) and African Americans between 19 and 39 (x = 24.3). Approximately 86% of Latinas and 7% of African Americans were married or living with a partner; 10.7% of Latinas and 53.8% of African Americans reported having health insurance; 60.7% of Latinas and 77.8% of African Americans had never heard about HPV. Following a brief presentation about cervical cancer and HPV, participants were questioned about the acceptability of a preventive HPV vaccine. Results: Overall, both groups indicated that an HPV preventive vaccine would be acceptable. However, African Americans were more skeptical, citing concerns about effectiveness and side effects. Another African American concern was whether vaccinated women would perceive themselves as being protected from HPV, leading them to increased promiscuity or unprotected sex. African Americans' motivating factors for vaccine use included receiving education/information about the vaccine, affordable prices, good results in trials, and knowing others who had already gotten vaccinated. Latina immigrants, on the other hand, unanimously stated that they would get the vaccine. However, they believed that multiple credible sources of information (educational talks, doctor's office, television, churches, and other women) needed to promote the vaccine before the Latino community at large would accept it. Conclusions: These findings suggest that unique educational strategies need to be developed, based on the needs and perceptions of the targeted audience, in order to achieve wide-spread acceptability of this vaccine. © 2007 Mary Ann Liebert, Inc.