The silver- and base metal-rich Caylloma epithermal district in the Tertiary volcanic belt of southern Peru has been worked intermittently since the Incaic period and has produced over 100 million ounces (Moz) of Ag. Intermediate-sulfidation mineralization is present in veins hosted by Miocene andesitic volcanic and volcaniclastic rocks, with minor ore in underlying folded Jurassic sedimentary basement. New 40 Ar/ 39 Ar dates give a host rock age of 20.30 ± 0.11 Ma (andesitic volcanic matrix), a hydrothermal alteration age of 18.35 ± 0.17 Ma (adularia in vein wall rock), and postmineralization ages of 11.8 ± 0.8 and 12.25 ± 0.07 Ma (sanidine and biotite from a rhyolite dome). Gangue minerals include quartz, calcite, rhodonite, rhodochrosite, pyrite and minor adularia, illite, barite, and helvite. Ore minerals include sphalerite, galena, chalcopyrite, and tetrahedrite. Hydrothermal alteration is pervasive in lava flows but weak and localized near veins in volcaniclastic rocks. Hydrothermal alteration types include silicification (quartz-adularia and quartz-illite) and propylitization (chlorite + calcite ± illite). Banded veins show four stages of mineral precipitation: (1) early sugary quartz, chalcedony, pyrite; (2) manganese minerals; (3) quartz + sulfides; and (4) late calcite + quartz. Cyclic bands in the manganese stage (early sulfides, coarse- to medium-grained quartz, late rhodonite + calcite + chalcedony) are a few millimeters to 5 cm thick and form ore bands up to 1 m thick. Veins occupy dextral normal faults (020°–050°, 45°–70° SE) and extension fractures (060°–090°, 70°–90° SE) and are 1 to 25 m wide and as much as several kilometers long. The veins display complex and multi-episodic filling with textures characteristic of open-space precipitation such as crustiform banding, symmetric banding, vugs, breccias, and cockade and comb textures. We present a structural model in which the principal veins formed in subparallel northeast-striking dextral-normal faults and related extension fractures within a northwest-striking structural corridor bounded by sinistral regional faults; second- and third-order veins formed by bookshelf sliding related to movement on higher-order, dominantly strike-slip faults. Slickenlines have low rakes (20°–50° SW), and fault-kinematic analysis suggests the extension axis was oriented 4°/330° and the shortening axis 55°/234°, in agreement with the strain field commonly proposed for the early-middle Miocene of southern Peru. Ore grade is discontinuous, with high-grade ore zones having strike lengths of tens to hundreds of meters and extending about 300 m downdip. Ore shoots in fault-hosted veins are narrow subvertical zones a few tens of meters wide (measured in the plane of the vein), separated by lower-grade ore zones. Ore shoots in extension fractures are shorter downdip and horizontally more continuous. Some ore shoots occur as half-cymoids that form along the main vein only in the hanging wall of synmineral transverse faults. Mineral composition and metal content are zoned horizontally and vertically; silver, base metals, and calcite and manganese minerals increase to the northeast and downward, and sulfide content increases gradually with depth. Shallower levels of the hydrothermal system are exposed to the west and southwest in the district. Evidence from sulfur isotopes and high-salinity fluid inclusions is consistent with a model in which magmatic fluids played a role in the hydrothermal system, introduced through channels of enhanced structural permeability. The cyclic nature of mineral precipitation with abrupt changes in mineralogy, textures, and fluid composition leads us to postulate that cyclic injections of magma-derived hydrothermal fluids occurred. Economic mineralization is estimated to have formed at a depth of about 650 m below the paleowater table, with a temperature of formation of ~270°C.