Syrian hamsters intracerebrally infected with tick-borne encephalitis (TBE) virus were used to study the correlation between virulence of the strains, their serotype, form and course of the disease, average survival time (AST) of hamsters, features of CNS pathomorphology, and the changes of values of cell-mediated and humoral immunity. Thirty one strains of TBE virus isolated in Siberia and Far East were studied. Virulence of the strains ranged from 100% to 5%, AST from 5 to 237 days. Hamsters developed acute lethal encephalitis, subacute encephalitis, or asymptomatic infection. Most virulent strains produced early and extensive lesions in the brain stem. In encephalitis with subacute course pathomorphological changes in the CNS developed slower and the brain stem was less involved. Each variant of TBE course was associated with a certain pattern of host immune response formed as early as the first day of infection. Highly virulent strains inducing acute encephalitis and 100% lethality within 5-9 days produced immune response characterized by high antigen reactivity of lymphocytes by the level of rosette-forming cells, marked specific sensitization in splenocyte migration-inhibition test, moderate antibody-producing cell reaction, increased thymus weight index, low values of nonspecific resistance with low levels of antihemagglutinins and virus-neutralizing antibody by the end of the first week. Different immunologic condition was associated with asymptomatic infection and increase of AST to 100-237 days.