The ability of tick-borne encephalitis (TBE) virus to cause programmed cell death (apoptosis) in viral infection of newborn mice and of two cell cultures is studied. The time course of virus antigen accumulation detected by enzyme immunoassay and of endonuclease fragmentation of nuclear DNA detected by agarose gel electrophoresis is compared. All three TBE strains differing by the source of isolation and biological characteristics can cause oligonucleosomal fragmentation of DNA of brain cells of two-day white mice and of SPEV cells in acute infection. In VERO-E6 cells the same three strains caused a latent infection; accumulation of virus antigen was not associated with endonuclease fragmentation of DNA or any other signs of cytopathic destruction. These data indicate that TBE virus can cause programmed cell death both in vitro and in vivo, which is apparently one mechanism of the cytopathic effect of the virus.