HL is characterized by significantly enlarged lymph nodes and the presence of rare Hodgkin and Reed-Sternberg cells. Pathogenesis is not fully understood. The increase in the disease risk can be associated with immunosuppression, HIV, parenchymal organ transplantation, autoimmune disorders, etc. The possibility of differentiating pathogenetic and protective immune responses associated with this disease will help understand the causes of the disease and the treatment prognosis. The study was aimed to determine the features of immune responses in HL depending on the disease duration and the circulating lymphocyte counts. A total of 134 patients with HL were assessed. The cytogram and phagocytosis were assessed in blood smears stained by the Wright-Giemsa procedure. The expression of lymphocyte markers in lymphocytes was determined using the indirect immunoperoxidase technique and flow cytometry. Serum levels of cytokines, immunoglobulins, autoantibodies and circulating immune complexes were assessed by enzyme immunoassay. Comparative analysis of the immune responses depending on peripheral blood leukocyte counts is provided. It has been found that prolonged HL course is associated with the decrease in the functionally active T cell counts, progressive neutropenia and monocytopenia, along with the increased activity of the reaginic reactions and autosensitization. In individuals with lymphocytopenia, mainly small lymphocytes die, the 3-fold decrease in the counts of such lymphocytes is observed; lymphocytopenia is associated with the deficiency of circulating T cells, both mature and immature, the concentrations of which decrease by 2.5–3 times, while B cell counts show no dramatic changes. The disease progression is associated with reduction of the lymphocyte homeostasis control by granulocytes and monocytes, along with progressive neutropenia and monocytopenia.