The prevalence of Epstein-Barr virus (EBV) and the recently identified Kaposi's sarcoma (KS)-associated herpesvirus (also designated human herpesvirus 8 [HHV-8]) was determined in oral lesions and oral neoplasms common to persons with human immunodeficiency virus (HIV) infection. Oral lesions were examined by polymerase chain reaction (PCR) for EBV and HHV-8 DNA and by Southern blot analysis for EBV clonality. EBV was detected by Southern blot in hairy leukoplakia lesions, in a subset of AIDS-related lymphomas, and in saliva from HIV-positive persons but not in pseudohairy leukoplakia lesions, oral aphthous ulcers, or oral KS lesions. EBV was detected, however, by PCR in most of the lesions, while HHV-8 was detected only in oral KSs. The absence of HHV-8 DNA in both the EBV-associated hairy leukoplakia lesions and in the EBV-associated AIDS-related lymphomas strengthens the etiologic relationship of EBV to these pathologies and the etiologic role of HHV-8 in KS.