The objective of this study was to assess whether the distribution of Borrelia burgdorferi, the causative agent of Lyme disease, and its vector tick Ixodes scapularis Say (Acari: Ixodidae) across Indiana is influenced by large-scale landscape features, specifically the proportion of forest within the surrounding landscape and the distance to water features such as lakes and major streams, Hunter-killed deer were checked for ticks in designated check-stations in the opening firearm hunting season between 2005 and 2007. Hunting locations for ≈3,600 deer were used in ArcGIS (ESRI, Redlands, CA) to examine the influence of forest and water features in the surrounding area on the occurrence of the tick and bacteria. In total, 82 of the 92 (89%) Indiana counties were sampled from 2005 to 2007. The proportion of tick-infested deer was 13.6, 15.8, and 25.5% in these years, respectively, There was a significant nonlinear response for I. scapularis to forest cover in 1 yr that indicated a greater probability of this tick presence at intermediate levels of forest area, Infested does were harvested in significantly more forested areas than bucks. No significant correlation was found neither between levels of forest area and B. burgdorferi nor between water bodies and both organisms.