The present study investigated 54 pediatric patients with acute Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM) in Japan. Most of the acute cases clustered within the first 5 years of life, and the peak incidence was observed at around 4 years of age. These patients were arbitrarily separated into three age groups (less than 3 years, 3-5 years, and 6-14 years). Fever, pharyngitis, lymphadenopathy and hepatomegaly were detected in more than 80% of all cases. Tonsillitis and splenomegaly were present in about 60% of cases. Skin manifestations and eyelids edema were less often detected in the older age group than in the young age groups. In addition to an increase of total white blood cell and lymphocyte counts in the peripheral blood, a significant increase in the percentage of CD3+ CD8+ HLA-DR+ T cells was always observed. Epstein-Barr virus seropositivity increased soon after birth and reached approximately 70% around 3 years of age. Close to 100% of the adult controls were EBV seropositive. The results suggest that EBV-induced acute IM is a disease of early childhood in Japan.