Three heterophile antibody tests and a test specific for IgM antibody to Epstein-Barr virus were evaluated during prospective studies of infectious mononucleosis. Specificity was judged by the frequency of false-positive results in sera of known qualities taken before illness; except for two patients bled during early, unrecognized illnes,, titers of greater than or equal to 1:40 were detected in 12% by the absorbed sheep red cell test, in 6.7% by the absorbed horse red cell test, and in none by the beef cell hemolysin test. None had IgM antibody specific for Epstein-Barr virus in sera obtained before illness. In addition, no rises in titer of heterophile antibody were detected by the horse cell test in 38 patients with proved rubella and/or influenza infection. In terms of sensitivity (indicated by the percentage of cases with diagnostic titers during infectious mononucleosis), 97% were positive by the Epstein-Barr virus IgM test, 96% by the horse cell agglutination test, 85% by the beef hemolysin test, and 81% by the sheep cell agglutination test. Persistence of antibody was judged by serial bleedings up to three years after illness; titers of heterophile antibody by the sheep agglutination and beef hemolysin tests as well as titers of IgM antibody to Epstein-Barr virus returned to normal in two to three months, whereas the horse cell heterophile test remained positive for a year or more in 75%. Inapparent and mild infections with Epstein-Barr virus resulted in the production of horse cell heterophile antibody in 48.4% of 122 subjects.

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In a 4-year prospective seroepidemiological study of infectious mononucleosis (IM) of one class of some 1400 cadets at the West Point Military Academy, sugceptibles and immunes were identified by the absence or presence of antibody to Epstein-Barr virus (EBV), the causative agent, and new infections by the appearance of antibody (seroconversion). On entry, about Va lacked EBV antibody, of whom some 20% became infected (seroconverted); about Vi of seroconverters developed definite, clinical and recognized IM. Psychosocial factors that significantly increased the risk of clinical IM among seroconverters included: 1) having fathers who were "overachievers"; 2) having a high level of motivation; 3) doing relatively poorly academically. The combination of high motivation and poor academic performance interacted in predicting clinical IM. Additional data on presence of elevated titers among seroconverters with inapparent disease and on length of hospitalization among cases of clinical IM revealed that these two additional indices of infection or illness could also be predicted from the same set of psychosocial risk factors.