We have evaluated the application for the diagnosis of infectious mononucleosis of several serologic criteria, including measurement of concentrations of IgM against viral capsid antigen (VCA) of Epstein-Bar virus (EBV) by ELISA, detection of heterophil antibodies and the presence of anti-VCA IgG in absence of IgG against nuclear antigen of EBV (EBNA). Such criteria were evaluated by using a board of sera obtained from cases who had clinically been diagnosed of infectious mononucleosis and identified in the laboratory as produced by EBV (84 sera) or cytomegalovirus (CMV) (9 sera). The measurement of anti-VCA IgM by any of the two tested methods is the best criteria for the serologic diagnosis of infectious mononucleosis. Positive anti-VCA IgM reactions were detected by IIF and ELISA in sera of patients with infectious mononucleosis-like syndrome due to cytomegalovirus, so an alternative method to the measurement of anti-VCA IgM is needed, the most adequate is the measurement of anti-VCA IgG in the absence of anti-EBNA IgG.