The effect of local geology and land-use practices on dissolved U was investigated by analysis of surface water and some springs in the Arkansas River valley of southeastern Colorado. Water samples were collected during a 2 week period in April, 1991. The rate of increase of U concentration with distance downriver increased markedly as the river flowed from predominantly undeveloped lands underlain by igneous and metamorphic rocks to agriculturally developed lands underlain by marine shale and limestone. An additional abrupt increase in dissolved U was observed along the section of river where discharge is often greatly reduced because of extensive diversions for irrigation and where remaining flow is largely composed of irrigation return water. Dissolved U in this last section of river and in most of its tributaries exceeded the proposed U.S. drinking water standard of 20 μ/L In water samples collected from agricultural areas dissolved U showed strong positive correlation with major dissolved constituents Na, Ca, Mg, and SO₄ that increase as a result of sulfate mineral dissolution and clay mineral ion-exchange reactions in weathered shale bedrock and shaley soils. Highly soluble minor and trace elements Cl, Li, B, Sr, and Se that are not subject to strong sorptive uptake or precipitation in this setting also correlated positively with U. These combined observations indicate that natural leaching of U-bearing shale bedrock and derivative soils, additional leaching of rock and soil by irrigation water, and evaporative concentration in a semi-arid climate can produce concentrations of dissolved U in surface water and shallow ground water that may threaten nearby drinking water supplies. Other agriculturally developed areas of the semi-arid Western U.S. with similar geology are likely to contain high concentrations of U in irrigation drain water.