Despite their usefulness in integrated pest management programs, concern that many introduced biological control agents will eventually begin using non-target species and detrimentally impact native populations is growing. The efficacy of two weevils (Rhinocyllus conicus and Trichosirocalus horridus) introduced in the U.S. against the Eurasian musk thistle (Carduus nutans) is countered by their impact on some native Cirsium thistles. Non-target feeding of these weevils may impact plant reproduction and plant populations. Because the biologies of these weevils are closely linked with musk thistle, the distribution of musk thistle populations may influence non-target activity. The use of geographic information systems (GIS) could be useful in analyzing the spatial relationships among musk thistle, weevil and native thistles by characterizing suitable habitats for each thistle species over a large spatial scale. In Spring 2004 a four-year study was initiated to: 1) characterize habitats where exotic thistles and native thistles can occur and 2) identify potential areas of non-target feeding using spatial analysis. The study area (ca. 4,800 km2) for the spatial analysis consisted of four counties in eastern Tennessee. Two native thistles (C. carolinianum and C. discolor) and two introduced thistles (C. nutans and C. discolor) were selected as model species, and thistle population localities documented from 2005 through 2007 were used to generate the model. Mahalanobis distance was used to identify suitable habitats for each thistle species. Other spatial data used to generate the models, model testing procedures and results and applications of these spatial analyses will be discussed.