Much of the Laurentian Great Lakes region is a mercury-sensitive landscape, in which atmospheric deposition and waterborne sources of mercury (Hg) have led to high concentrations of bioavailable methylmercury (MeHg) in predatory fish and piscivorous wildlife. Efforts since the early 1990s have established the common loon (Gavia immer) as the primary avian indicator for evaluating the exposure and effects of MeHg in North America. A regional Hg dataset was compiled from multiple loon tissue types and yellow perch (Perca flavescens), a preferred prey fish species for loons. Hg exposure in loons and perch was modeled to develop male and female loon units (MLU and FLU, respectively), standardized metrics that represent the estimated blood Hg exposure of a male or female loon for a given loon territory or water body. Using this common endpoint approach to assess loon Hg exposure, the authors demonstrate spatial trends in biotic Hg concentrations, examine MeHg availability in aquatic ecosystems of the Great Lakes region in relation to landscape-level characteristics, and identify areas with potentially significant adverse reproductive impacts to loons and other avian piscivores. Based on 8,101 MLUs, seven biological Hg hotspots were identified in the Great Lakes region. Policy-relevant applications are presented.