Mercury (Hg) is a globally distributed pollutant that poses considerable risks to human and wildlife health. Over the past 150 years since the advent of the industrial revolution, approximately 80 percent of global emissions have come from anthropogenic sources, largely fossil fuel combustion. As a result, atmospheric deposition of Hg has increased by up to 4-fold above pre-industrial times. Because of their isolation, remote high-elevation lakes represent unique environments for evaluating the bioaccumulation of atmospherically deposited Hg through freshwater food webs, as well as for evaluating the relative importance of Hg loading versus landscape influences on Hg bioaccumulation. The increase in Hg deposition to these systems over the past century, coupled with their limited exposure to direct anthropogenic disturbance make them useful indicators for estimating how changes in Hg emissions may propagate to changes in Hg bioaccumulation and ecological risk. In this study, we evaluated Hg concentrations in fishes of high-elevation, sub-alpine lakes in the Wallowa-Whitman National Forest in northeastern Oregon and western Idaho. Our goals were to (1) assess the magnitude of Hg contamination in small-catchment lakes to evaluate the risk of atmospheric Hg to human and wildlife health, (2) quantify the spatial variability in fish Hg concentrations, and (3) determine the ecological, limnological, and landscape factors that are best correlated with fish total mercury (THg) concentrations in these systems. Across the 28 study lakes, mean THg concentrations of resident salmonid fishes varied as much as 18-fold among lakes. Importantly, our top statistical model explained 87 percent of the variability in fish THg concentrations among lakes with four key landscape and limnological variables— catchment conifer density (basal area of conifers within a lake’s catchment), lake surface area, aqueous dissolved sulfate, and dissolved organic carbon. The basal area of conifers within a lake’s catchment was by far the most important variable explaining fish THg concentrations, with an increase in THg concentrations of more than 400 percent across the forest density spectrum. Across all study lakes, fish THg concentrations ranged from 0.004 to 0.438 milligrams per kilogram wet weight (mg/kg ww). Only a single individual fish sample exceeded the U.S. Environmental Protection Agency’s (USEPA) human health tissue residue criteria of 0.3 mg/kg ww. However, 54 percent of fish (N=177) exceeded the more stringent tissue residue criteria (0.04 mg/kg ww) adopted by the Oregon Department of Environmental Quality to better protect subsistence fishers. Additionally, 2 and 10 percent of fish exceeded levels associated with reduced common loon reproduction and behavior, respectively. Whereas 25 and 68 percent of fish sampled exceeded concentrations deemed protective of mink and kingfisher, respectively. These results suggest that THg concentrations may be present in these lakes at levels associated with ecological risk. It is important to note however, that accurate inference on potential impairment cannot be made within the context of this study design and further research is needed to better quantify these risks.