The risk of Borrelia transmission to humans in the eastern United States is dependent on the density of infected nymphal Ixodes scapularis ticks. While many local and regional studies have estimated I. scapularis density, there has never been a large-scale field-based study using a common, standardized methodology. To develop a nationwide spatial risk model for I. scapularis-borne Borrelia, we designed a four-year survey of I. scapularis covering its known geographic range. We report the results of the first season of sampling. We measured the density of host-seeking I. scapularis nymphs by drag sampling of closed-canopy deciduous forest habitats in 95 locations spaced among two-degree quadrants covering the entire United States east of the 100th meridian. Sampling was done in five standardized transects at each site and repeated 4 to 6 times during the summer of 2004. We evaluated the relationship between the spatial and temporal patterns of tick density and temperature, water vapor profile and enhanced vegetation index products from NASA moderate resolution imaging spectroradiometer (MODIS), at 250-1000m resolution. We controlled for local weather conditions by recording temperature, humidity and wind at sampling. Data from this first season will be used to plan future sampling, and data from subsequent years will be used to validate model predictions and improve accuracy. A model for I. scapularis density derived from such a large-scale field study will be a major advance toward the production of an accurate continuous surface map of human risk for infection with I. scapularis-borne Borrelia for the United States.