Epstein-Barr virus (EBV) is a highly prevalent virus, transmitted via saliva, 
which often causes asymptomatic infection in children but frequently results in 
infectious mononucleosis in adolescents. Heterophile antibody tests, including 
the Monospot test, are red cell or latex agglutination assays, which detect 
antired cell antibodies produced as part of a polyclonal antibody response 
occurring during EBV infection. Heterophile antibody tests are rapid, cheap and 
specific tests that can be performed from the onset of symptoms of infectious 
mononucleosis. In adolescents, heterophile antibody tests have high specificity 
and sensitivity in the diagnosis of primary acute EBV infection. However, the 
tests have low sensitivity and low negative predictive value in young children 
and are not useful under the age of 4. Heterophile tests may be positive in 
other viral infections, autoimmune disease and haematological malignancies, but 
do not appear to be positive in primary bacterial infection. Virus-specific 
serology is required in children under the age of 4 or if an older child is 
heterophile negative. Virus-specific serology allows diagnosis and the pattern 
of positivity and negativity enables the clinician to stage the EBV infection. 
Virus-specific serology appears to have better sensitivity in young children, 
but there is cross-reaction with other herpesvirus infections, a longer 
turnaround time and it is more expensive to perform. Further research is needed 
to establish which children benefit from and hence require testing for 
heterophile antibodies, the cost-effectiveness of EBV investigations and whether 
heterophile titres have predictive value for the severity of infection and the 
likelihood of complications.