Fifty-one cases of malignant and non-malignant oral diseases were investigated for Epstein-Barr virus (EBV). EBV DNA was detected by polymerase chain reaction analysis in 2 of 4 papillomas, but not in other tissues including 36 squamous cell carcinomas and 4 leukoplakias. The copy numbers of EBV DNA in the two positive samples were estimated to be 120 and 36 per cell, respectively. Intense EBV DNA signals were detected on papilloma cells by in situ hybridization. DNAs for the benign and malignant types of human papilloma virus were not detected in papilloma tissues. The present results suggest that EBV is a causative agent of oral papilloma.