A number of viruses, most notably herpes virus type 2, have been suggested as etiological agents of cervical neoplasia. Recent studies with human papillomaviruses, however, have demonstrated a remarkable association of a subgroup of these viruses with about 90% of benign, preinvasive and invasive lesions of the cervix and anogenital tract. The oncogenic potential of papillomaviruses has been demonstrated both in laboratory animals and in cultured cells. Furthermore, susceptibility to certain human papillomaviruses has been associated with a recessive genetic defect that results in squamous cell carcinoma of the skin. The human papillomaviruses are difficult to study, however, because of the lack of an animal model, difficulty in developing a tissue culture system permissive for their replication, and a lack of understanding of their biology. Current understanding of the natural history of anogenital neoplasia may provide insights into the mechanisms the host uses to cope with potentially oncogenic human papillomaviruses.