In a retrospective study of selected hyperplastic and neoplastic epithelial lesions of wild, exotic, and domestic animals, paraffin sections from 438 biopsies and 15 necropsies were screened for the presence of papillomavirus structural antigens, using the peroxidase-antiperoxidase technique. Viral antigens were detected in tissues from 9 of 21 different mammalian, 1 of 5 avian, and 0 of 2 reptilian species. The latter tissues were histopathologically classified as papillomas, fibropapillomas, and fibromas and of canine origin (n = 6), squamous cell carcinoma. Virus could be readily detected by transmission electron microscopy in lesions that contained numerous nuclei which stained positively by the peroxidase-antiperoxidase technique.