This paper presents preliminary results in our investigations of the biological (abiotic and biotic) and non-biological causes of the spatial heterogeneity and temporal change of tick-borne encephalitis (TBE), both within and between Estonia, Latvia, and Lithuania. Spatial analysis revealed that the land cover and precise seasonal patterns of climatic indices (temperature and normalized difference vegetation index) can explain 55% of the observed spatial variation in TBE incidence over the period 1993-98 across all the Baltic States. Temporal analysis of climatic variables indicates a very specific change in spring temperature conditions from 1993 onwards that could enhance the transmission of TBE virus. Further time series analysis of climate, together with analysis of biotic factors, socio-economic conditions, and human behaviour is being undertaken to explain the epidemiological patterns more fully.