Segments of the Clinch River in Virginia have experienced declining freshwater mussel populations during the past 40 years, while other segments of the river continue to support some of the richest mussel communities in the country. The close proximity of these contrasting reaches provides a study area where differences in climate, hydrology, and historic mussel distribution are minimal. The USGS conducted a study between 2009 and 2011 to evaluate possible causes of the mussel declines. Evaluation of mussel habitat showed no differences in physical habitat quality, leaving water and sediment quality as possible causes for declines. Three years of continuous water-quality data showed higher turbidity and specific conductance in the reaches with low-quality mussel assemblages compared to reaches with high-quality mussel assemblages. Discrete water-quality samples showed higher major ions and metals concentrations in the low-quality reach. Base-flow samples contained high major ion and metal concentrations coincident to low-quality mussel populations. These results support a conceptual model of dilution and augmentation where increased concentrations of major ions and other dissolved constituents from mined tributaries result in reaches with declining mussel populations. Tributaries from unmined basins provide water with low concentrations of dissolved constituents, diluting reaches of the Clinch River where high-quality mussel populations occur.