A high incidence of initial infection with human papillomavirus (HPV) was previously reported in a cohort of 608 women monitored at 6-month intervals for 3 years. Risk factors for subsequent infections with different HPV types and whether antibodies against HPV-16 virus-like particles (VLPs) protected against these infections were examined. Subsequent infections with HPV are very common. Seventy percent of women acquired a different HPV type within 24 months of the initial infection. Risk factors included being nonwhite, having an increased number of male sex partners, and having had a new male sex partner. Use of oral contraceptive pills was protective. A sustained high level of IgG antibody to HPV-16 VLPs was associated with reduced risk for subsequent infection with HPV-16 and its genetically related types (i.e., HPV-31, -33, -35, -52, and -58).