Hodgkin's disease (HD) typically has a bimodal age distribution and is less common than non-Hodgkin's lymphoma in the pediatric age group, especially in very young children. Recent reports described a high prevalence of Epstein-Barr virus (EBV) in HD from developing countries in both adult and pediatric populations. In this series, we studied with immunohistochemical analysis 44 cases of pediatric HD from the United States to investigate the association with EBV in developed countries and to determine which subtypes occur in this group. The 44 cases (40 boys, 4 girls; male-to-female ratio, 10:1) were categorized as nodular lymphocyte predominance in 16 (36.4%) of 44; nodular sclerosis in 13 (29.5%); and mixed cellularity in 4 (9.1%). Eleven of the cases were difficult to subclassify by the usual morphologic and immunophenotypic criteria. Of these, eight (18.1%) were designated interfollicular HD, and three were classified as HD "not otherwise specified." EBV LMP was positive in 38.6% of cases: 5 (38.5%) of the 13 with nodular sclerosis; 3 (75%) of the 4 with mixed cellularity; 1 (6.0%) of the 16 with nodular lymphocyte predominance; 7 (87.5%) of the 8 with interfollicular HD; and 1 (33.3%) of the 3 with HD "not otherwise specified." There was a strong association between the age of the patient and EBV expression. In children 4 years or younger, all of the 3 cases were LMP positive; in the 5- to 9-year-old age group, 8 (61.5%) of 13 were LMP positive; and in the 10- to 15-year-old group, only 21.4% were positive. Our results confirm the male predominance in pediatric HD and show an association with EBV, especially in the youngest patients and with the mixed cellularity and interfollicular subtypes. Most, but not all, cases of pediatric HD can be subclassified by traditional criteria.