Epstein-Barr virus (EBV), a member of the herpesvirus group, is the etiologic agent of infectious mononucleosis. EBV infections are difficult to diagnose in the laboratory since the virus does not grow in standard cell cultures. The majority of infections can be recognized, however, by testing the patient's serum for heterophile antibodies (rapid latex slide agglutination test; eg, MONOS / Infectious Mononucleosis Rapid Test, Serum). Heterophile antibodies usually appear within the first 3 weeks of illness, but then decline rapidly within a few weeks. The heterophile antibody, however, fails to develop in about 10% of adults, more frequently in children, and almost uniformly in infants with primary EBV infections. Most of these heterophile antibody negative cases of infectious mononucleosis-like infections are due to cytomegalovirus, but in 1 series of 43 cases, EBV was the cause in 7. In cases where EBV is suspected but the heterophile antibody is not detected, an evaluation of EBV-specific antibodies (eg, IgM and IgG antibodies to EBV viral capsid antigen: VCA) and antibodies to EBV nuclear antigen (EBNA) may be useful. The EBV EIA tests that detect antibodies to the EBV VCA and early antigen (EA) are more sensitive than heterophile antibody tests.