In industrialized populations, Hodgkin's disease (HD) has an initial peak in young adulthood, whereas in economically developing populations the initial peak occurs in childhood. This pattern resembles that of infection with poliovirus and suggests an infectious cofactor in the etiology. Serologic studies have linked Epstein-Barr virus (EBV) to young adult and adult HD, and viral nucleic acids and antigens have been detected in a subset of Hodgkin's tumor specimens. To investigate the association of childhood HD with EBV we studied tumor specimens from 11 children treated in Honduras and 25 children treated in the United States using in situ hybridization and antigen detection techniques. Among the patients from Honduras, tumor specimens from all cases were EBV positive. Among the patients from the United States, tumor specimens from six of seven patients with mixed cellularity histology, 2 of 15 with nodular sclerosis histology, and neither of two patients with lymphocyte-predominant histologies were EBV positive. These findings support the hypothesis that EBV contributes to the pathogenesis of HD in children, particularly in mixed cellularity HD, and raises the possibility that there are important geographic, racial, or ethnic factors in the EBV association with HD.