Salt in the upper Colorado River is of concern for a number of political and socioeconomic reasons. Salinity limits in the 1974 U.S. agreement with Mexico require the United States to deliver Colorado River water of a particular quality to the border. Irrigation of crops, protection of wildlife habitat, and treatment for municipal water along the course of the river also place restrictions on the river's salt content. Most of the salt in the upper Colorado River at Cisco, Utah, comes from interactions of water with rock formations, their derived soil, and alluvium. Half of the salt comes from the Mancos Shale and the Eagle Valley Evaporite. Anthropogenic activities in the river basin (for example, mining, farming, petroleum exploration, and urban development) can greatly accelerate the release of constituents from these geologic materials, thus increasing the salt load of nearby streams and rivers. Evaporative concentration further concentrates these salts in several watersheds where agricultural land is extensively irrigated. Sulfur and oxygen isotopes of sulfate show the greatest promise for fingerprinting the geologic sources of salts to the upper Colorado River and its major tributaries and estimating the relative contribution from each geologic formation. Knowing the salt source, its contribution, and whether the salt is released during natural weathering or during anthropogenic activities, such as irrigation and urban development, will facilitate efforts to lower the salt content of the upper Colorado River.