The etiology of Hodgkin's disease (HD) is unknown, but a growing body of evidence suggests that the Epstein-Barr virus (EBV) plays a role in a proportion of cases. Clonal EBV genomes have been detected in affected tissues, and EBV has been localized to Reed-Sternberg (RS) cells, the putative malignant cells in HD. EBV latent genes, including the EBER RNAs and the latent membrane protein, LMP-1, are expressed by RS cells. These data suggest that EBV is playing a role in the pathogenesis of HD; however, it is clearly not involved in all cases. Using in situ hybridization, we can detect EBV within the RS cells in approximately 40% of cases. Epidemiological data suggest that HD is a heterogeneous condition and the distribution of EBV-associated cases is not random. Studies from several groups indicate that mixed cellularity cases are more likely to be EBV-associated than nodular sclerosis cases. Our data further suggest that the majority of pediatric and older cases of HD are EBV-associated, whereas the RS cells in young adult cases only rarely harbor EBV. We therefore speculate that another virus is responsible for the young adult peak in incidence which is seen in developed countries.