Perchlorate (ClO4-) has been detected widely in groundwater and soils of the southwestern United States. Much of this ClO 4- appears to be natural, and it may have accumulated largely through wet and dry atmospheric deposition. This study evaluates the isotopic composition of natural ClO4- indigenous to the southwestern U.S. Stable isotope ratios were measured in ClO4 - (δ18O, Δ17O, δ 37Cl) and associated NO3- (δ 18O, Δ17O, δ15N) in groundwater from the southern High Plains (SHP) of Texas and New Mexico and the Middle Rio Grande Basin (MRGB) in New Mexico, from unsaturated subsoil in the SHP, and from NO3--rich surface caliche deposits near Death Valley, California. The data indicate natural ClO4- in the southwestern U.S. has a wide range of isotopic compositions that are distinct from those reported previously for natural ClO4- from the Atacama Desert of Chile as well as all known synthetic ClO4 -. ClO4- in Death Valley caliche has a range of high Δ17O values (+8.6 to +18.4 %), overlapping and extending the Atacama range, indicating at least partial atmospheric formation via reaction with ozone (O3). However, the Death Valley δ37Cl values (-3.1 to -0.8 %) and δ18O values (+2.9 to +26.1%) are higher than those of Atacama ClO4-. In contrast, ClO4- from western Texas and New Mexico has much lower Δ17O (+0.3 to +1.3%), with relatively high δ37Cl (+3.4 to +5.1 %) and δ18O (+0.5 to +4.8 %), indicating either that this material was not primarily generated with O 3 as a reactant or that the ClO4- was affected by postdepositional O isotope exchange. High Δ17O values in ClO4- (Atacama and Death Valley) are associated with high Δ17O values in NO3-, indicating that both compounds preserve characteristics of O3-related atmospheric production in hyper-arid settings, whereas both compounds have low Δ17O values in less arid settings. Although Δ17O variations in terrestrial NO3- can be attributed to mixing of atmospheric (high Δ17O) and biogenic (low Δ17O) NO3-, variations in Δ17O of terrestrial ClO4- are not readily explained in the same way. This study provides important new constraints for identifying natural sources of ClO4- in different environments by multicomponent isotopic characteristics, while presenting the possibilities of divergent ClO4- formation mechanisms and(or) ClO4- isotopic exchange in biologically active environments.