A total of 151 unselected malignant and nonmalignant lymphoid tissue samples were surveyed by Southern blotting for the presence of Epstein-Barr virus (EBV) DNA. Eight of 28 Hodgkin's disease (HD) samples (29%) had detectable EBV DNA. Both nodular sclerosis and mixed cellularity histologic results were positive. The tumor type with the next highest frequency, 8%, was diffuse large cell lymphoma. The presence of EBV DNA in some HD biopsies suggests that EBV may be a factor in the pathogenesis of this disease. Alternatively, its presence may be secondary to the immune deficiency characteristic of HD. The clonal B-lymphocyte expansions reported in some cases of HD may result from EBV infection.