Infectious mononucleosis syndrome, characterized in typical cases by fever, sore throat, tonsillar exudates, cervical adenopathies and atypical lymphocytosis is associated in most cases to Epstein-Barr virus (EBV) infection. Other potential causes for this syndrome are acute cytomegalovirus (CMV), Human Immunodeficiency Virus, Toxoplasma gondii or Human Herpes virus 6 infection. These alternative etiologies evolve with a modified clinical picture that includes sometimes leukopenia or rash. Diagnosis of EBV is easily accomplished by atypical lymphocytosis (> 10%), positive heterophil antibodies and IgM antibodies directed against the EB viral capsid antigen (VCA). The latter is needed for cases without positive heterophil antibodies. Acute CMV infection is the second most important cause and can be diagnosed by CMV antigen detection, PCR or shell vial culture of blood samples, although experience with these tests among immunocompetent patients in primary care settings is sparse. Acute primary HIV infection is an important cause for this syndrome and should not be neglected when other causes are discarded. Third or fourth generation HIV ELISA tests, p24 antigen or HIV-PCR detection in blood samples allow recognition of this agent from the second or third week of inoculation. T. gondii and human herpes virus 6 infection can be diagnosed by serological methods. Evolution of EBV or CMV infection is favorable with infrequent complications