Six oral papillomas and 7 oral leukoplakias were studied with genus-specific antibodies against detergent-disrupted papillomaviruses. Indirect immunofluorescence staining was applied to frozen sections. Distinct nuclear staining of superficial keratinocytes was seen in 5 of 6 oral papillomas, 2 of 5 homogenous leukoplakias, and in 2 cases of nodular leukoplakia, one of these showing transition into an invasive carcinoma. Papillomavirus antibodies offer a new way to detect and localize papillomaviruses in epithelial hyperplasias. The relevance of the immunomorphological identification of papillomavirus-associated antigens is discussed with special reference to the molecular hybridization technique.