Infectious mononucleosis is caused by Epstein-Barr virus (EBV), a member of the human herpesvirus family. A prodromal period of 3-5 days includes headache, malaise, myalgia, and fatigue. The classic clinical triad consists of fever, pharyngitis, and cervical adenopathy. Malaise, sweats, sore throat, anorexia, nausea, and headache are the most common symptoms. Myalgias, ocular muscle pain, chest pain, and rhinitis are not infrequent. Photophobia and arthralgias may also occur.

The child appears generally ill with readily apparent cervical adenopathy in most cases. Splenomegaly typically occurs during the second and third week. Hepatomegaly rarely develops. The classic mononucleosis syndrome occurs almost without exception in teenagers and young adults.

Children treated with ampicillin or penicillins often develop exanthematous rashes following initiation of therapy.

Other rare complications include upper airway obstruction, hemolytic anemia, thrombocytopenic purpura, severe granulocytopenia, pneumonia, meningoencephalitis, recurrent aseptic meningitis (Mollaret's meningitis), Guillain-Barré syndrome, Miller Fisher syndrome (bilateral ptosis, total ophthalmoplegia, cerebellar symptoms, and hyporeflexia), psychosis, Bell palsy, myocarditis, pericarditis, coronary artery spasm, pancreatitis, nephritis, and fulminating hepatic necrosis.

Neurological complications, airway obstruction, and splenic rupture are the most common causes of death in otherwise healthy persons. Gastrointestinal symptoms, palatal petechiae, and insidious onset are associated with a prolonged recovery period. Occasionally jaundice, arthritis, and pneumonitis are seen.

When a child with x-linked lymphoproliferative disease is infected with EBV, the child will not develop a normal serological response to infection and can have hepatitis that progresses to liver failure. Survivors may have chronic mononucleosis and progression to lymphoma.