Seroepidemiological and molecular biological studies have established an association of Hodgkin's disease with Epstein-Barr virus. Recently, Epstein-Barr virus genomes and gene products have been detected in the neoplastic cells of approximately 50% of cases, most notably the latent membrane protein, which has transforming potential. However, Epstein-Barr virus was not restricted to neoplastic cells. In situ hybridization, employing probes for the small Epstein-Barr virus-encoded nuclear RNAs EBER1 and -2, helped to precisely characterize phenotype and distribution of all latently Epstein-Barr virus-infected cells, indicating the presence of usually small numbers of Epstein-Barr virus-infected, but latent membrane protein-negative, non-malignant B-cells of polyclonal origin in lymph nodes from Hodgkin's disease patients and normal controls. In contrast, the neoplastic cells and the Epstein-Barr virus genomes expressing latent membrane protein in these cells appear to be monoclonal in nature, which points to specific immunological deficiencies in Hodgkin's disease patients and suggests that Epstein-Barr virus may contribute to the etiology of a significant proportion of Hodgkin's disease cases.