Programmed cell death (PCD) is a fundamental process regulating immune homeostasis. During acute viral infections PCD of lymphocytes by apoptosis is necessary for removing the excess of activated antigen-reactive T cells and down-regulation of the immune response. On the other hand, apoptosis is the key mechanism of elimination of viral-infected cells. At the present time there is virtually no data on mechanisms of immune regulation during human hantavirus infections. In this study we examined the dynamic of PBL Fas and FasL expression, the first-step dead caspase-8, -2, -9 and effector caspase-3, -7 and -10 activity in freshly isolated PBL lysates, and anti-CD3-induced PBL mitogenic response and apoptosis in patients with Puumala virus (PUUV) associated hemorrhagic fever with the renal syndrome (HFRS). Data reported summarize the initial demonstration of increased Fas/FasL and activation of the initializing (caspase-2, -8 and -9) and the effector caspase-3, -7 and -10 in PBML during acute and convalescent phases of the hantavirus infection. The suppressed anti-CD3 mitogenic response and increased anti-CD3-induced apoptosis were also observed. Although more study needs to be done to determine the role of hantavirus and hantavirus induced pathways in PBML apoptosis, our data suggests that the immune system reacts to hantavirus infection, as to many other virus infections, by activation of apoptosis. These reactions of the immune system could be directed to preserve immune homeostasis, developing the most effective immune protection, and to eliminate cells infected with virus.