A marked increase in tick-borne encephalitis (TBE) incidence has been observed in Europe during the last 2 decades. Hypothetical causes include global climatic fluctuations, human-induced environmental changes, and socio-economic changes. These factors are thought to be disproportionately relevant in different geographical areas. To date, epidemiological studies of this phenomenon were based primarily on aggregated data, and little is known about TBE dynamics on the detailed geographical scale. This study is aimed at the subregional variations of incidence of TBE in the Czech Republic. The methodology of spatial statistics was applied. Over 13,000 cases of TBE, registered 1971-2007, were pinpointed on a GIS map and analysed for density variations in both time and space. Selected areas were studied in detail, using time series analysis. These analyses revealed that the incidence of TBE was highly variable both across the country and over the study period. Although the aggregate total of reported cases were generally increasing, local trends were divergent. A detailed study of one endemic area (that one with the highest case density level) showed that heterogeneities are detectable, even on a very fine geographical scale. There was no evident spatial coherence of the TBE trends; and some adjacent areas showed quite differing trends. However, countrywide coherence was demonstrated for quasi-octennial fluctuations in the TBE series, associable with the North Atlantic oscillation. The possible influences of both various climatic and population covariates upon TBE occurrence are discussed. However, the geographical heterogeneity of the disease trends, at such a fine spatial scale, cannot be explained satisfactorily by fluctuations in climatic or socio-economic conditions.