Mononucleosis-like disease may be caused by the cytomegalovirus (CMV) as well as the classic mononucleosis of the Epstein-Barr virus (EBV). Both viruses are members of the herpes virus family.

Mononucleosis caused by EBV is the most frequently encountered type and is responsible for approximately 85% of infectious mononucleosis cases. The infection is often transmitted by saliva. While it happens most often in 15- to 17-year-olds, the infection may occur in any age, being most often diagnosed between the ages of 10 and 35.

Infectious mononucleosis may begin slowly with fatigue, malaise, headache, and sore throat. The sore throat becomes progressively worse, often with enlarged tonsils covered with a whitish-yellow fibrinous exudate. The lymph nodes in the neck are frequently enlarged and painful. A pink measles-like rash may occur in approximately 1 out of 10 individuals with mono.

Four out of five patients with mononucleosis who are given ampicillin or amoxicillin for their "throat infection" will develop the rash, but it is significantly darker and denser than the rash in those not given medication. Symptoms of mononucleosis gradually subside over a period of weeks to a month. The disease is generally self-limited.

Risk factors other than age are not known. The incidence in the United States is 2 out of 1,000 in adolescents and young adults. It is significantly lower for the entire U.S. population. Age of infection varies from country to country. For example, in Africa most individuals have been infected by age 3 years, an age at which there are very few symptoms.

Chronic EBV infection may be associated with some types of cancer. In Africa, EBV is associated with Burkitt's lymphoma, while in China and among the Eskimos, EBV may be associated with cancers of the nose and throat (nasopharyngeal carcinoma). In organ transplant patients it can cause post-transplant lymphoproliferative disease (PTLD), a type of lymphoma.