Tick-borne encephalitis (TBE) is one of the most frequent arthropod-transmitted viral diseases in Europe. Different vaccines against TBE-virus have been developed; a thimerosal-free and also albumin-free vaccine [Ticovac (Baxter Hyland Immuno, Vienna)] was approved in 2000. Contrary to previous experience, 779 cases of fever occurred following the first vaccination of children under 15 years of age and in 62 children febrile convulsions were even observed. Consequently, the composition of the vaccine was changed and albumin was again added [FSME-Immun (Baxter Vaccines, Vienna)] in 2001. The new Encepur Kinder (Chiron-Behring, Marburg) from 2002 is a TBE-vaccine for children without any protein as stabilizer but with a relatively high concentration of sucrose, while the former vaccine Encepur K from 1991 contained polygeline as the stabilizer. The induction of the immune system by the different TBE virus vaccines was compared in an in vitro test in order to find an explanation for the unexpected fever attacks. Whole blood was stimulated with complete vaccine suspension, and TNF-alpha, IL-1beta, IL-6, and IL-8 were determined from heparin/EDTA-plasma and culture supernatants. It was shown that Ticovac and the new Encepur Kinder can induce relatively high amounts of TNF-alpha and lower amounts of IL-1beta. An increase of both cytokines was first observed following an incubation of 4 hours, with a maximum after 15 hours. Concentrations returned to base-line values within 26 hours. The behaviour of both cytokines correlates with the febrile phases in children up to two years old. Albumin or other proteins like polygeline and also immunoglobulins prevented a rise of cytokines.