Human papillomavirus (HPV) type 6 capsids were produced by recombinant vaccinia viruses and used in a capture ELISA to screen 901 human sera from three studies of genital HPVs. The highest seroprevalence was observed among subjects with recurrent genital warts. In a population-based case-control study of genital warts, 26 (58%) of 45 women with recurrent genital warts were seropositive compared with 19 (19%) of 101 control women with no history of genital warts (odds ratio, 6.5; 95% confidence interval, 3.0, 14.1). Among a cohort of pregnant women, 7 (88%) of 8 with recurrent warts were seropositive compared with 24 (30%) of 79 pregnant women with no such history. A significant association between seropositivity to HPV-6 capsids and the detection of HPV-6/11 DNA from genital specimens by polymerase chain reaction was also observed. Men with genital warts were less likely to be seropositive than were women with genital warts, and a positive association between the number of sex partners and seropositivity was observed among only the female university students.