The indices of immune response were studied in 68 patients with infectious mononucleosis caused by the Epstein-Barr virus (35 males, 33 females) aged 18 to 30 years. Materials and methods. The content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50, sHLAI, sCD54) has been studied with enzyme immunoassay using monoclonal antibodies Mab IC0-20 and polyclonal antibodies to the antigens of the mononuclear cells of the peripheral blood. The control group included 60 healthy volunteers matched for age and sex with the main group. The aim of this study is the assessment of the content of soluble forms of differentiation antigens in patients with infectious mononucleosis caused by Epstein-Barr virus, depending on gender, age, severity of illness, comorbidities, laboratory values, the presence of viral DNA, as well as a demonstration of their value in predicting the course and outcome of the disease and the efficacy of antiviral and immunocorrecting therapy. In patients with negative results of DNA indication of EBV a significant increase in the content of soluble forms of differentiation antigens characterizing the adhesion of leukocytes (sCD18), the activity of T-lymphocytes (sCD50), the recognition of foreign antigens (sHLAI) in the blood in comparison with patients with a positive DNA indication of EBV was determined. Conclusion. According to the results of this performed work the criterion for an adequate immune response in patients with infectious mononucleosis caused by the Epstein-Barr virus was found to be the increase of the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54). In patients with exanthema, tonsillar syndrome, leukocytosis, elevation of transaminases and the presence of antibodies to capsid antigen (a/VCAIgM) the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54), was higher than in patients without such symptoms. In the treatment with cycloferon in patients with cyclic course of EBV infectious mononucleosis the content of sHLAI and sCD54 at 2nd-4th weeks of treatment increased by 1.5-2 times compared with the corresponding values before treatment. In patients with reactivation of the disease monotonically low indices of all studied soluble forms of differentiation antigens persisted over the 4 weeks during patients following up. In patients with infectious mononucleosis caused by Epstein-Barr virus, the dynamics of sHLAI and sCD54 after 2-4 weeks of treatment serves as secondary efficacy endpoint of antiviral, immunomodulatory therapy and the formation of the cyclic course of the disease.