Cloned DNAs of 21 different papillomaviruses which naturally infect mammals and one bird papillomavirus were compared for relative homology by Southern blot hybridization. Blots were carried out under low (Tm-40 degrees), medium (Tm-33 degrees), and high (Tm-22 degrees) stringency conditions. At higher stringency, human papillomaviruses cross-hybridized with each other reflecting species-specific similarities. Bovine papillomavirus types 1, 2, 5, European elk papillomavirus, and deer papillomavirus also cross-hybridized at higher stringencies probably reflecting the association of these viruses with fibroblast-prolific lesions. The hybridization data presented here may be useful in future classification attempts. They are also useful as a guide in the selection of papillomavirus DNA probes for analysis of extracts from warts and tumors.