HPV 2a is commonly associated with verrucae vulgares, whereas HPV 57 was detected in mucosal lesions of the maxillary sinus and the genital tract, as well as in cutaneous lesions. The complete DNA sequences of HPV 2a and HPV 57 were determined. The HPV 2a genome consists of 7860 base pairs and the HPV 57 genome contains 7861 base pairs. On the nucleotide level an 83% homology between the two sequences could be ascertained. Compared to other HPVs they have a high G/C-content (HPV 2a: 48.8%, HPV 57: 50.1%). The genomic organization of both viruses complies with that of other sequenced HPVs. Significant sequence divergence between the HPV 2a and HPV 57 genomes was found in the long control region (LCR), as well as in the early-late-region (ELR). The latter varies in size between the cutaneous (72 to 103 nucleotides) and the mucosal HPVs (252 to 584 nucleotides). According to the sizes of the ELRs of HPV 2a (377 nucleotides) and HPV 57 (478 nucleotides), as well as DNA sequence comparisons, these two viruses could be grouped with the so-called mucosal HPVs. In a search for possible tissue-specific elements, a common amino acid motif, thr-thr/asp-pro-ala-ile/valile/leu was found in the L2 of all mucosal HPVs, as well as in HPV 2a and 57. The L2 of the cutaneous types contain the motif val-ser/thr-arg-thr-gln-tyr.