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The aim of this investigation was to localize natural foci of tickborne encephalitis (TBE) in Switzerland by means of two approaches. (1) Sera of foresters, who are particularly exposed to TBE, were examined, restricting serum collection to the Plateau between the Lake of Constance and the Lake of Geneva. (2) Virus isolations were performed on 8600 ticks (Ixodes ricinus) collected all over the country. In four regions natural foci of varying size were detected: (1) in the northern parts of the Canton of Zurich in conjunction with the southern parts of the Canton of Schaffhausen, (2) in the region of Horgen on the Lake of Zurich, (3) in the region of Thoune, and (4) in the marshy region situated between the Lakes of Neuchâtel, Bienne and Morat. The morbidity rate in foresters varied from 0-5%, and rose to 12-16% in regions with a known concentration of natural foci. The infection rates in ticks average 0.1%, but, depending on the regions where ticks were collected, maximum rates of 1% were attained.