Recent reports have questioned the validity of dissolved trace element concentrations reported by the U.S. Geological Survey's National Stream Quality Accounting Network (NASQAN) as well as by other water-quality monitoring programs. To address these concerns and to evaluate the NASQAN protocols, the U.S. Geological Survey undertook the Mississippi River Methods Comparison Study. We report here the major results and implications of this study. In particular, we confirm the possible inaccuracy of previous NASQAN dissolved trace element data. The results suggest that all steps of the NASQAN protocol (sampling, processing, and analysis) require revision, though the sample filtration step appears to be of particular concern.