An antiserum prepared by immunization of a rabbit with sodium dodecyl sulfate-disrupted virions from a pool of plantar warts was cross-reactive with virus-positive papillomas of other animal species by both indirect immunofluorescence tests on frozen sections of wart tissues and peroxidase-antiperoxidase tests of sections of Formalin-fixed tissues. The antiserum stained plantar warts, common warts, and skin lesions of epidermodysplasia verruciformis, all from humans; bovine fibropapilloma, experimentally produced with bovine types 1 and 2; and transmissible canine oral papillomas. The staining was localized to nuclei of the upper granular layers of the peithelium and was similar in distribution to the pattern produced by antiserum specifically prepared against that papillomavirus. The antiserum did not stain virus-negative warts, or cells infected with simlan virus 40, human polyomavirus BK, and murine polyomavirus. These data suggested that papillomaviruses share a common internal antigen unrelated to a similar antigen described previously for the polyomaviruses (which include simian virus 40 and polyomavirus subgroups).