Abstract Epithermal mineralization in the El Indio-Pascua belt, a world-class Au-Ag-Cu district located along the Chile-Argentina frontier, formed in the late Miocene within an actively uplifting tectonic block of the Cordillera Principal. Previous studies have demonstrated a spatial and temporal relationship between epithermal processes and a series of regional erosional surfaces (pediplains) for all the major deposits in the belt. Ore deposition occurred beneath the 12.5 to 14 Ma Azufreras-Torta pediplain but near the head of actively incising 6 to 10 Ma Los Ríos pediment valleys. New isotopic and paragenetic data for several major deposits (Pascua-Lama, Tambo, El Indio) suggest that this geomorphologic setting had a significant impact on the processes that produced preore alteration, ore deposition, and postore processes. Barren, preore alteration of late Oligocene to early Miocene age occurs throughout the belt and is well-developed in the vicinity of the major ore deposits. This alteration is of a hypogene advanced argillic type, and isotopic data for alunite and associated sulfide minerals are characteristic of a magmatic-hydrothermal origin. Alunite-pyrite pairs, where available, suggest depositional temperatures of 190° to 350°C. All economic mineralization in the belt is of an epithermal type and is dominated by high-sulfidation—state mineral assemblages. At both Pascua-Lama and Tambo, alunite is intergrown with, or host to, much of the precious metal mineralization. Isotopic data are consistent with a magmatic-hydrothermal origin for much of this alunite, and ore deposition resulted from the boiling of magmatic-dominated fluid at temperatures of ca. 200° to 300°C. A transition from magmatic-hydrothermal to magmatic steam-dominated processes is evident in both systems, and at Tambo this transition is associated with significant Au deposition. Large steam-heated alteration blankets developed above these mineralized centers during this time, although the isotopic signature of this alteration is not typical of most steam-heated zones and is characterized by magmatic-dominated fluid. In contrast to Pascua-Lama and Tambo, alunite at El Indio is restricted to banded alunite sulfide veins that postdate most other mineralized veins in the district. Constraints on mineralization are more difficult to determine for this deposit due to its wide age range (<6.2–7.8 Ma) and different ore styles. A lithologic contact between the Tilito Formation volcanic rocks and overlying andesites of the Escabroso Group most likely enhanced fluid mixing and suppressed widespread boiling of magmatic fluid, although evidence for local boiling in the late, banded alunite sulfide veins is recognized. Overall, isotopic studies and other features of these deposits suggest that magmatic-hydrothermal processes and epithermal ore deposition were strongly influenced by pediment erosion and semiarid climatic conditions. The dominance of magmatic condensates for the duration of the major mineralizing systems, even in near-surface alteration zones, is consistent with an arid climate and limited availability of meteoric water. Telescoping of alteration assemblages and the occurrence of supergene alteration to appreciable depths below the surface suggest drops in the paleowater tables during late stages of the hydrothermal systems. At both Tambo and Pascua-Lama, fluid inclusion and mineralogic evidence for fluid boiling during the main stages of mineralization is recognized. Similarly, in both these systems, a transition to magmatic steam-dominated processes also argues for rapid changes in hydrostatic pressures. In the absence of large volcanic edifices and the potential for topographic collapse, erosion at the head of the Los Ríos pediment valleys, where most deposits are located, is thought to have had a major influence on high-level fluid-flow regimes. Rapid draining of the outflow zones by local catastrophic erosion may have promoted boiling in the upflow zones and allowed lateral outflow at lower topographic levels, thereby significantly modifying the nature of these richly mineralized systems.