Mercury is a ubiquitous, persistent toxicant found in the environment. In water, mercury bioaccumulates up the food chain and leads to high concentrations in fish. Consumption of contaminated fish is the major source of exposure to mercury in the US. The objective of this study was to enroll persons living in areas selected by the Environmental Protection Agency (EPA) to have high mercury concentrations and who consume at least 6 oz of locally caught fish per week to determine the feasibility of monitoring future trends among a population identified as highly exposed. Blood samples were collected at time of interview and analyzed for mercury. Participants (n = 287) were enrolled from North Carolina, Maryland, and South Dakota. Participants reported eating an average of five servings of fish per week. The overall geometric mean for total mercury was 0.75 ?g L?1, with North Carolina having the highest mean level (2.02 ?g L?1). Overall, 42% of the study population had levels greater than the US geometric mean 0.83 ?g L?1. The number of servings of fish consumed was not found to be associated with bloodmercurylevels. We were able to identify some persons with elevated mercury concentrations living in areas identified by EPA; however, identifying and monitoring a highly exposed population over time would be challenging.