Contamination of fish populations with methylmercury is common in the region of the Laurentian Great Lakes as a result of atmospheric deposition and methylation of inorganic mercury. Using fish mercury monitoring data from natural resource agencies and information on tissue concentrations injurious to fish, we conducted a screening-level risk assessment of mercury to sexually mature female walleye (Sander vitreus), northern pike (Esox lucius), smallmouth bass (Micropterus dolomieu), and largemouth bass (Micropterus salmoides) in the Great Lakes and in interior lakes, impoundments, and rivers of the Great Lakes region. The assessment included more than 43,000 measurements of mercury in fish from more than 2000 locations. Sexually mature female fish that exceeded threshold-effect tissue concentrations of 0.20 μg g(-1) wet weight in the whole body occurred at 8% (largemouth bass) to 43% (walleye) of sites. Fish at 3% to 18% of sites were at risk of injury and exceeded 0.30 μg g(-1) where an alteration in reproduction or survival is predicted to occur. Most fish at increased risk were from interior lakes and impoundments. In the Great Lakes, no sites had sexually mature fish that exceeded threshold-effect concentrations. Results of this screening-level assessment indicate that fish at a substantive number of locations within the Great Lakes region are potentially at risk from methylmercury contamination and would benefit from reduction in mercury concentrations.