Stable isotope (??D and ??18O) signatures of three principal groundwater recharge areas in the 21,000-km2 upper Klamath Basin are used to infer recharge sources for aquifers in the interior parts of the basin. Two of the principal recharge areas, the Cascade Range on the western and southern margin of the basin and uplands along the eastern margin, are defined by mean annual precipitation that exceeds approximately 60 cm. A third recharge area coincides with the extensive irrigation canal system in the south central part of the basin. The stable isotope signature for Cascade Range groundwater falls near the global meteoric water line (GMWL). The stable isotope signature for the groundwater of the eastern basin uplands also falls near the GMWL, but is depleted in heavy isotopes relative to the Cascade Range groundwater. The stable isotope signature for water from the irrigation canal system deviates from the GMWL in a manner indicative of fractionation by evaporation. Groundwater provenance was previously unknown for two aquifers of interest: that supplying deep (225-792 m), large-capacity irrigation wells along the Oregon-California border, and that of the geothermal system near Klamath Falls. Groundwater produced by the deep irrigation wells along the Oregon-California border appears to be a mixture of eastern-basin groundwater and water with an evaporative isotopic signature. The component with an evaporative isotopic signature appears in some places to consist of infiltrated irrigation water. Chloride data suggest that much of the component with the evaporative isotopic signature may be coming from an adjacent subbasin. After accounting for the 18O shift common in geothermal waters, isotope data suggest that the geothermal groundwater in the upper Klamath Basin may emanate from the eastern basin uplands. Findings demonstrate that stable isotope and chloride data can illuminate certain details of a regional groundwater flow system in a complex geologic setting where other hydrologic data are ambiguous. ?? 2007 Elsevier B.V. All rights reserved.