Water-quality sampling was conducted regularly at stream sites within or near the Powder River structural basin in northeastern Wyoming and southeastern Montana during water years 2001-05 (October 1, 2000, to September 30, 2005) to characterize water quality in an area of coalbed natural gas development. The U.S. Geological Survey, in cooperation with the Wyoming Department of Environmental Quality, characterized the water quality at 22 sampling sites in the Tongue, Powder, Cheyenne, and Belle Fourche River drainage basins. Data for general hydrology, field measurements, major-ion chemistry, and selected trace elements were summarized, and specific conductance and sodium-adsorption ratios were evaluated for relations with streamflow and seasonal variability. Trend analysis for water years 1991-2005 was conducted for selected sites and constituents to assess change through time. Average annual runoff was highly variable among the stream sites. Generally, streams that have headwaters in the Bighorn Mountains had more runoff as a result of higher average annual precipitation than streams that have headwaters in the plains. The Powder River at Moorhead, Mont., had the largest average annual runoff (319,000 acre-feet) of all the sites; however, streams in the Tongue River drainage basin had the highest runoff per unit area of the four major drainage basins. Annual runoff in all major drainage basins was less than average during 2001-05 because of drought conditions. Consequently, water-quality samples collected during the study period may not represent long-term water-quality conditions for all sites. Water-quality characteristics were highly variable generally because of streamflow variability, geologic controls, and potential land-use effects. The range of median specific-conductance values among sites was smallest in the Tongue River drainage basin. Median values in that basin ranged from 643 microsiemens per centimeter at 25 degrees Celsius (µS/cm at 25°C) on the Tongue River to 1,460 µS/cm at 25°C on Prairie Dog Creek. The Tongue River drainage basin has the largest percentage of area underlain by Mesozoic-age and older rocks and by more resistant rocks. In addition, the higher annual precipitation and a steeper gradient in this basin compared to basins in the plains produce relatively fast stream velocities, which result in a short contact time between stream waters and basin materials. The Powder River drainage basin, which has the largest drainage area and most diverse site conditions, had the largest range of median specific-conductance values among the four major drainage basins. Median values in that basin ranged from 680 µS/cm at 25°C on Clear Creek to 5,950 µS/cm at 25°C on Salt Creek. Median specific-conductance values among sites in the Cheyenne River drainage basin ranged from 1,850 µS/cm at 25°C on Black Thunder Creek to 4,680 µS/cm at 25°C on the Cheyenne River. The entire Cheyenne River drainage basin is in the plains, which have low precipitation, soluble geologic materials, and relatively low grad...