Changes in the activity of Na(+),K(+)-ATPase during infection of SPEV cells with tick-borne encephalitis (TBE) virus were studied in preparations of cell membranes and directly in the culture and the effect of this enzyme activity on the penetration of TBE virus in the cells and production of virus-specific proteins investigated. The highest activity of the enzyme was observed directly after challenge and during the 5th and 6th hours of infection, whereas the lowest was recorded during the second and third hours and 24 h postinfection. A similar decrease in the activity of this ATPase was observed in the brain cells of infected mice. Ouabain and low (0 degree C) temperature prevented the virus penetration in the cells, which indicates that this process is energy-dependent. Inhibition of Na(+),K(+)-ATPase led to a drop in the production of virus-specific protein.