In September 2005, Chronic Wasting Disease (CWD) was confirmed in a 2.5-year-old male white-tailed deer in central Hampshire County as part of routine surveillance initiated in West Virginia in 2002. While awaiting confirmation of this first known occurrence in the state, the West Virginia Division of Natural Resources (WVDNR) initiated its CWD Response Plan. The goal of this plan is to guide decision-making in defining distribution and frequency of the disease in deer populations and attempt to prevent the spread of CWD to cervids in uninfected areas. In late September 2005, 206 deer were killed by sharpshooters and sampled for CWD within an 8-km radius of where the initial positive case was found. Four additional deer tested positive during this sampling period. Sampling 2170 hunter-killed bucks taken during the 2005 and 2006 hunting seasons resulted in one deer testing positive. Sampling an additional 85 and 100 deer with WVDNR sharpshooters in spring of 2006 and 2007, respectively, resulted in seven additional deer testing positive. Sampling was conducted within 3.2 km of previously known CWD positive samples. Most deer testing positive for CWD collected by sharpshooters were females. Increased surveillance in Hampshire County and adjacent counties will continue into the foreseeable future. Personnel, time, financial demands of initial response, public relations, and epidemiology are discussed.