The effects of lithologic changes on the water quality of the Kuskokwim River, Alaska, were evaluated by the U.S. Geological Survey in June 1997. Water, suspended sediments, and bed sediments were sampled from the Kusko-kwim River and from three tributaries, the Holitna River, Red Devil Creek, and Crooked Creek. Dissolved boron, chromium, copper, manganese, zinc, aluminum, lithium, barium, iron, antimony, arsenic, mercury, and strontium were detected. Dissolved manganese and iron concentrations were three and four times higher in the Holitna River than in the Kusko-kwim River. Finely divided ferruginous materials found in the graywacke and shale units of the Kuskokwim Group are the probable source of the iron. The highest concentrations of dissolved strontium and barium were found at McGrath, and the limestone present in the upper basin was the most probable source of strontium. The total mercury concentrations on the Kuskokwim River decreased downstream from McGrath. Dissolved mercury was 24 to 32 percent of the total concentration. The highest concentrations of total mercury, and of dissolved antimony and arsenic were found in Red Devil Creek. The higher concentrations from Red Devil Creek did not affect the main stem mercury transport because the tributary was small relative to the Kuskokwim River. In Red Devil Creek, total mercury exceeded the concentration at which the U.S. Environmental Protection Agency (USEPA) indicates that aquatic life is affected and dissolved arsenic exceeded the USEPA's drinking-water standard. Background mercury and antimony concentrations in bed sediments ranged from 0.09 to 0.15 micrograms per gram for mercury and from 1.6 to 2.1 micrograms per gram for antimony. Background arsenic concentrations were greater than 27 micrograms per gram. Sites near the Red Devil mercury mine had mercury and antimony concentrations greater than background concentrations. These concentrations probably reflect the proximity to the ore body and past mining. Crooked Creek had mercury concentrations greater than the background concentration. The transport of suspended sediment-associated trace elements was lower for all elements in the lower river than in the upper river, indicating storage of sediments and their associated metals within the river system.