Of 68 children 2 to 15 years of age who had clinical signs compatible with infectious mononucleosis, 38had serologic evidence for a primary Epstein-Barr virus infection. Using qualitative and quantitative techniques for detection of heterophil antibodies, 50% of the 38 patients had positive reactions in rapid slide agglutination tests with sheep RBC stromata, and 79% in slide tests with horse RBC. In the quantitative tests, 79% reacted in the ox cell hemolysin tests, 82% in the Paul-Bunnell-Davidsohn test, and 95% in the immune-adherence hemagglutination test. The percentages of reactors were lowest in the 2 to 5-year-old groups and highest in the 11-to 15-year-old patients. Thus, depending on the assay used, the percentage of heterophil antibody responses in the youngest patients may differ only slighty form that seen in adolescents or yong adults. Although the ranges of titers oberved with the three quantitative assays and in the three age groups were similar, the geometric mean titers incrased three-to eightforld from the youngest to the oldest group of patients. None of the 30 patients with mononucleosis-like illnesses not associated with EBV had positive heterophil reactions. Thus, rapid slide tests using horse RBC serve to confirm a diagnosis of infectious mononucleosis in the majority of pediatric patients, and EBV-specific serodiagnostic tests are needed mainly to identify heterophil negative cases of infectious mononucleosis and to separate them from mononucleosis-like illenesses caused by other agents.