Tick-borne encephalitis virus isolates from widely separated geographic regions of the USSR, six isolates from Hungary and one from France were compared with the European and Far Eastern prototype viruses. Peptide mapping by limited proteolysis yielded similar patterns for five selected isolates from the USSR. All isolates from Hungary and France exhibited the same reactivity pattern with a panel of 16 protein E-specific monoclonal antibodies, whereas 10 out of 12 isolates from the Soviet Union showed minor differences at certain epitopes. However, no correlation between geographic origin of the isolates and their antigenic structure was observed. No statistically significant difference in the degree of protection was detected when mice were immunized with the European prototype vaccine and challenged with three selected Asian isolates and one from the European part of the USSR.