Discovered in 1553, the Fresnillo mine in central Mexico has produced approximately 18 t Au, 8830 t Ag, 690 000 t Pb, 925 600 t Zn, and 74 000 t Cu (data for production from 1921 to 1984 inclusive). Ore has been mined from an oxide capping near surface and from unoxidized veins, mantos, and chimneys to a depth of 1 km along a strike length of 4 km. Ore zones at depth, in the northwest portion of the mine, are spatially related to a quartz monzonite porphyry stock, which intrudes a sequence of Mesozoic marine sediments that is overlain by terrestrial rhyolites. Manto and chimney mineralization followed development of skarn around the intrusion and was cut, in turn, by the veins that contain the bulk of the ore. The veins cut the quartz monzonite stock. Manto and chimney mineralization is characterized by partial replacement of the Mesozoic sedimentary rocks with axinite, hedenbergite, quartz, carbonate, sulphides, sulphosalts, sulpharsenides, and sulphantimonides. Brecciation preceded replacement in the chimney bodies. One of the largest replacement orebodies, the Cueva Santa Branch Manto in the central part of the mine, contains an orthogonal fracture set formed during antiformal folding. Trends in grade distribution throughout the manto follow the orthogonal fractures, which are filled by quartz and sulphides. Silver/base-metal ratios show marked peaks where manto mineralization abuts against major veins. Fluid-inclusion filling temperatures and salinities are high in ore zones adjacent to the quartz monzonite stock at a depth of 1 km: mean filling temperature is approximately 320 °C (range 230–370 °C), salinity ranges from 4 to 12 eq. wt.% NaCl. Fluid inclusions from ore near surface exhibit lower filling temperatures (a mean of 235 °C and a range of 210–290 °C) and lower salinity (< 1 eq. wt.% NaCl). The data are consistent with a reduction in temperature and with dilution as the hydrothermal fluids flowed away from the intrusive porphyry.δ34S values for sphalerite, galena, and chalcopyrite from deeper and intermediate levels in the mine range from −6.1 to −3.5‰. Calculated δ34SΣS is approximately 0‰, suggesting a magmatic sulphur source. Lead isotopic ratios obtained from galena-bearing vein, manto, and chimney samples throughout the mine fall on a line defined by 34 deposits in northern Mexico with slope of 0.092 ± 0.017 in the 208Pb/204Pb versus 207Pb/204Pb system. The lead data indicate that felsic igneous processes extracted the metal from a Precambrian basement source; this was followed by concentration within mineralized zones during hydrothermal activity.