In Germany, 100-300 autochthonous clinical TBE cases have been recorded annually. There are high-risk areas in Bavaria and Baden-Wuerttemberg and ongoing low-risk areas in Hesse, Thuringia, and the Rhineland-Palatinate and single cases in Saxony. In order to be able to evaluate the epidemiological changes described here, it must be mentioned that a new definition of TBE risk areas was introduced on the district level in 1998 in Germany and in 2001 with the new Infection Protection Act (Infektionsschutzgesetz) which states that TBE is a notifiable disease. This led to the replacement of earlier surveillance systems and to many changes to data collection. In 1998 63 country and town districts were TBE risk areas, in 2001 79 and in 2002 86. There were new risk districts within Bavaria and Baden-Wuerttemberg and outside these regions in Thuringia, Hesse and the Rhineland-Palatinate. An interesting trend was observed in TBE epidemiology. The TBE incidence in Bavaria and Baden-Wuerttemberg has been stable on a high level for years; outside these areas it has steadily been climbing (Odenwald, Thuringia). On the basis of epidemiological data on TBE from the eastern part of Germany since 1960, it is obvious that major changes in virus activity in TBE risk areas also occurred in the past, the explanation of which has remained a matter for speculation. The epidemiological situation in the different risk areas for TBE in Germany was found to vary considerably, if one considers the surveillance data of the last 40 years. 1. Establishment of completely new low-risk areas. 2. Reactivation of formerly active areas with endemic latency. 3. High-risk areas with stable viral activity over long periods. 4. High-risk areas which have expanded and merged with low-risk areas. 5. High-risk areas which have developed into endemic areas or become inactive. High-risk TBE areas from 1960-1975 (i.e. Mecklenburg-Western Pomerania) have since completely disappeared. There were, at the same time, high-risk areas in Thuringia which had only become latent and have now obviously become active again. The Odenwald demonstrated growing virus activity in the 1990s. These changes in TBE activity in German risk areas over more than the last 40 years are presented schematically. This ongoing number of risk areas is certainly linked to the notification obligation and greater public awareness. Nevertheless, any effects of ecological and climatic changes on the natural foci cannot be ruled out nor can changes in human leisure behaviour. Local weather conditions also have a major effect on the TBE incidence. Warm and dry summers may cause low tick activities, rainy summers may lead to low exposure rates of human beings. Even changes in forms of agricultural production prompted by different political structures probably have an impact as do economic constraints which may lead to lower vaccination and higher exposure rates. Regular, systematic virus prevalence measurements from 1997 to 2002 in field-collected ticks in German high-risk areas do not indicate any risk increase nor do they suggest a downward trend. Studies on virus prevalence in questing versus partially engorged ticks indicate that we neither exactly know nor understand the real quantitative relations between the virus and the host. In a first study, virus prevalence in Ixodes ricinus removed from humans was examined. Humans which were exposed in some districts near Passau in Bavaria. In the autumn of 2001, virus prevalence of unengorged free-living nymphs (n = 820) in this area was 0.38 (0.08-1.1)% and of adults (n = 90) 1.17 (0.03-6.38)%. Surprisingly, virus prevalence in partially engorged ticks from the same area collected during the same period was significantly higher (nymphs, n = 86, 6.9% and adults, n = 129, 9.3%). Virus-positive partially engorged ticks were only found in districts known as risk areas. Nucleotide and deduced amino acid sequence data of the PCR products have confirmed the presence of virus prototype Neudoerfl only.