The linear virion form of Epstein-Barr virus (EBV) DNA has variable numbers of direct tandem 500 bp repeats at each terminus. The terminal restriction endonuclease fragments and the fused terminal fragments in the intracellular episomal form are heterogeneous in size, and vary by increments of 500 bp. The structure of the termini of EBV in carcinomas of the nasopharynx and the parotid gland was compared with the EBV termini in monoclonal and polyclonal tissues or cell lines. A single band representing the EBV joined termini was detected in each of the carcinomas and in the monoclonal lymphoid proliferations. Polyclonal cell lines contained multiple forms of the joined termini. The detection of a homogeneous episomal population suggests that EBV-associated epithelial malignancies are clonal expansions of a single EBV-infected progenitor cell.