The complete nucleotide sequence of the HPV 59 DNA genome, isolated from a vulvar intraepithelial neoplasia, was determined. It consists of 7896 nucleotides. A comparative analysis of this sequence with the sequences of other HPV types revealed the closest homology to HPV 18 (71%), HPV 45 (70%), and HPV 39 (69%). Phylogenetic analysis of the complete L1 ORFs of HPV 59 and other papillomaviruses exclusively groups all HPVs which have been detected in mucosal lesions into one major branch. This major branch, in turn, includes two specific subgroups containing all high risk viruses associated with malignant mucosal lesions. The motif in the L2 ORF thr-thr-pro-ala-val/ile-leu/ile-asp/asn-val/ile, an extension of a previously reported mucosal motif, is highly conserved in all HPV types detected in mucosal lesions, whereas it is totally absent in those viruses exclusively associated with cutaneous lesions.