Human papillomavirus type 16 (HPV-16) is causally involved in the pathogenesis of genital neoplasia, but important details of the natural history of infection and disease are not yet understood. Many individual HPV-16 DNA isolates differ by characteristic point mutations. In a study of the HPV-16 variants from genital lesions of 32 married couples, HPV-16 was detected in both the husband and the wife in 8 couples. Of these, 4 demonstrated identical HPV-16 variants between husband and wife, and 4 had mismatching HPV-16 variants. Five of 31 biopsies showed simultaneous presence of two different HPV-16 variants. The data suggest that sexual transmission of HPV-16 does occur, but with low infectivity, and that HPV-16-related premalignant lesions are frequently polyclonal.