In 2013, the U.S. Geological Survey (USGS) National Water-Quality Assessment Program (NAWQA) and USGS Columbia Environmental Research Center (CERC) will be collaborating with the U.S. Environmental Protection Agency (EPA) National Rivers and Streams Assessment (NRSA) to assess stream quality across the Midwestern United States. The sites selected for this study are a subset of the larger NRSA, implemented by the EPA, States and Tribes to sample flowing waters across the United States (http://water.epa.gov/type/rsl/monitoring/riverssurvey/index.cfm). The goals are to characterize water-quality stressors—contaminants, nutrients, and sediment—and ecological conditions in streams throughout the Midwest and to determine the relative effects of these stressors on aquatic organisms in the streams. Findings will contribute useful information for communities and policymakers by identifying which human and environmental factors are the most critical in controlling stream quality. This collaborative study enhances information provided to the public and policymakers and minimizes costs by leveraging and sharing data gathered under existing programs. In the spring and early summer, NAWQA will sample streams weekly for contaminants, nutrients, and sediment. During the same time period, CERC will test sediment and water samples for toxicity, deploy time-integrating samplers, and measure reproductive effects and biomarkers of contaminant exposure in fish or amphibians. NRSA will sample sites once during the summer to assess ecological and habitat conditions in the streams by collecting data on algal, macroinvertebrate, and fish communities and collecting detailed physical-habitat measurements. Study-team members from all three programs will work in collaboration with USGS Water Science Centers and State agencies on study design, execution of sampling and analysis, and reporting.