The "mono syndrome" is an acute febrile disease of older children and young adults which involves the lymphatic system and is characterized hematologically by the presence of 50% or more lymphocytes and monocytes and 10% or more atypical lymphocytes. Epstein-Barr virus (EBV) causes over 90% of the syndrome, cytomegalovirus (CMV) about 5% to 7%, and Toxoplasma gondii less than 1%. Viral hepatitis, adenovirus, rubella, and herpes simplex are rare causes. Only EBV produces classical heterophile-positive infectious mononucleosis. This article reviews the epidemiological and clinical features of this syndrome.