Introduction Chronic infectious mononucleosis is a clinical entity recognized 15 years ago with clearly defined serological criteria: high titres of IgG Epstein-Barr virus (EBV) virus capsid antigen (VCA), IgG EBV early antigen without IgG Epstein-Barr nuclear antigen (EBNA) antibodies. Material and methods This follow-up study lasted for 2 years and included 100 acute infectious mononucleosis patients who were investigated every 6 months. Apart from physical examination we evaluated history, complete blood count and liver function together with 5 commercial ELISA tests: IgM EBV VCA, IgG EBV VCA, IgG EB NA, IgG EBV EA and IgA EBV EA. Results Although malaise and fatigue with cervical lymphadenopathy were the most frequent symptoms, their statistical significance was not established. All laboratory analyses were completely normal during the follow-up period, but there were four patients with acute hepatitis due to hepatitis A virus and adenoviruses. After 6 months of acute illness, two patients without IgG EB NA antibodies who were candidates for chronic disease, presented no other serological findings for chronic disease. It was confirmed that they had delayed serological response due to EBV infection, because one year later they had a completely normal immune status on EBV infection. Conclusion Chronic infectious mononucleosis seems to be an extraordinary event after acute disease. This conclusion corresponds with literature reports of sporadic cases of this disease.