It is not known if current chemical and biological monitoring methods are appropriate for assessing the impacts of growing industrial development on ecologically sensitive northern waters. We used a multitrophic level approach to evaluate current monitoring methods and to determine whether metal-mining activities had affected 2 otherwise pristine rivers that flow into the South Nahanni River, Northwest Territories, a World Heritage Site. We compared upstream reference conditions in the rivers to sites downstream and further downstream of mines. The endpoints we evaluated included concentrations of metals in river water, sediments, and liver and flesh of slimy sculpin (Cottus cognatus); benthic algal and macroinvertebrate abundance, richness, diversity, and community composition; and various slimy sculpin measures, our sentinel forage fish species. Elevated concentrations of copper and iron in liver tissue of sculpin from the Flat River were associated with high concentrations of mine-derived iron in river water and copper in sediments that were above national guidelines. In addition, sites downstream of the mine on the Flat River had increased algal abundances and altered benthic macroinvertebrate communities, whereas the sites downstream of the mine on Prairie Creek had increased benthic macroinvertebrate taxa richness and improved sculpin condition. Biological differences in both rivers were consistent with mild enrichment of the rivers downstream of current and historical mining activity. We recommend that monitoring in these northern rivers focus on indicators in epilithon and benthic macroinvertebrate communities due to their responsiveness and as alternatives to lethal fish sampling in habitats with low fish abundance. We also recommend monitoring of metal burdens in periphyton and benthic invertebrates for assessment of exposure to mine effluent and causal association. Although the effects of mining activities on riverine biota currently are limited, our results show that there is potential for effects to occur with proposed growth in mining activities.