Abstract This paper discusses the possible genetic relationship between two ore deposits in the Nevados del Famatina mining district, Argentina: Nevados del Famatina Cu-Mo-Au porphyry deposit and La Mejicana Cu-Au high-sulfidation epithermal deposit. The porphyry system crops out in three open annular areas dominated by porphyritic rocks at elevations between 4000 and 4800 m; the epithermal vein system is peripheral to the porphyry and crops out on adjacent ridges at elevations above 4500 m. The spatial, geologic, petrographic and geochronologic parameters suggest that there is a genetic relationship between the two deposits, and detailed mineralogic, fluid inclusion, and stable isotope studies and preliminary thermodynamic modeling provide additional support. The hydrothermal fluids, from which the ore, gangue, and alteration minerals were deposited, were dominated by magmatic volatiles, with admixture of groundwaters during the later vein stages in both the porphyry and epithermal deposits. Representative pressures, temperatures, and salinities decreased over the paragenetic stages of the porphyry and with increasing elevation in the late vein stages of the porphyry and epithermal systems. The fluids also became progressively more oxidized, more acidic, and lower in sulfur gas activity over the same stages and elevations. The temperature, pressure, and fluid composition (salinity, redox state, sulfur gas, acidity) inferred for the epithermal system are similar to those calculated for the last stage of the porphyry deposit. There are striking similarities in detailed mineralogy between the last porphyry vein stage and the epithermal veins. All available data support the hypothesis that the porphyry and high-sulfidation deposits are transitional and genetically related.