Between 1976 and 1982, 113 children aged 6 months to 16 years with documented Epstein-Barr virus-induced infectious mononucleosis were studied prospectively, and in most instances serially. An unexpected finding was the large number of young children, less than 4 years old, with this disease. Children with infectious mononucleosis, in particular the very young, tended to have more rashes, significant neutropenia, abdominal pain (older children only), and possible hepatosplenomegaly than have been reported in adult patients. The intensity of the characteristic relative atypical lymphocytosis found in peripheral blood was age-related; it was less in the very young. Findings of failure to thrive, otitis media, and episodes of recurrent tonsillopharyngitis appeared to be unique or more closely associated with childhood disease. Complications such as thrombocytopenia with hemorrhagic manifestations, significant airway obstruction, and neurologic problems occurred more frequently whereas jaundice occurred less frequently than noted in adult patients. Six children, all less than 4 years old, developed pneumonia during the disease course. The increased availability of Epstein-Barr virus-specific testing should continue to expand our knowledge of this disease in children of all ages.