Human papillomavirus (HPV) type 5 is associated with benign and malignant lesions of the disease epidermodysplasia verruciformis (EV). Because of the strong correlation between the presence of HPV-5 and malignant progression in these patients, we have elucidated the nucleotide sequence of the HPV-5 genome. The size of the HPV-5 genome is 7746 nucleotides and its organization is similar to that of other papillomaviruses. The HPV-5 genome exhibits extensive sequence homology with another EV-associated papillomavirus, HPV-8, although HPV-5 appears to contain at least one additional open reading frame.