Epstein-Barr virus (EBV) infection is characterized by a benign course except for the rare variants which include chronic active disease (EBV-CAD) and secondary hemophagocytic syndrome (EBV-sHPS). sHPS is a life-threatening disorder associated with severely impaired immune response regulation. The pathogenesis is based on the activation of cytotoxic Т-lymphocytes, NK-cells and macrophages with overproduction of proinflammatory cytokines and ineffective systemic inflammatory response. The most common manifestations are persistent febrile fever, moderate cytopenia, cytolytic and cholestatic syndromes, and multiple organ failure. One of the most effective agents for the control of hyperergic reaction is etoposide. The present paper reports the outcomes of treating 5 EBV-sHPS patients and 1 EBV-CAD patient. All of them showed fever, liver dysfunction, hypofibrinogenemia, and cytopenia. In sHPS patients, pronounced hyperferritinemia was identified. At the time of submitting the present paper, 3 patients with no evident disease were still followed up.