The Santo Nino vein is a classic example of silver-base metal epithermal mineralization and is one of the principal orebodies in the Fresnillo district. The extensive vein structure once represented a major conduit for fluids in the shallow upflow region of a magma-generated hydrothermal system. Continuous fracturing and vein opening permitted recurring passage of fluids which resulted in four stages of mineralization; the first three contain quartz, sulfides, and sulfosalts, whereas the final stage is dominated by calcite.Fluid inclusion studies on the quartz, calcite, and sphalerite indicate that mineralizing solutions ranged between 170 degrees to 260 degrees C and 9 to 60 bars pressure and were close to or at boiling conditions throughout the mineralizing period. The best estimate of the paleosurface elevation is approximately 100 m above the present-day surface. However, considerable vertical fluctuation of the piezometric surface of boiling solutions apparently occurred during regional hydrothermal activity; for the period in which the Santo Nino vein was mineralized, the piezometric boiling surface was situated well below the paleosurface, possibly by as much as 150 to 200 m.Three distinct fluids were identified on the basis of freezing data and oxygen and hydrogen isotope compositions. Quartz-saturated solutions were dilute, averaging 2 equiv wt percent NaCl and less than 4 wt percent CO 2 . These solutions evolved from extensive exchange reactions between country rock and deep circulating meteoric waters (delta 18 O water = 3.9 to 7.7ppm, delta D = -43 to -74ppm), but may additionally include some magmatic waters. Stage IV calcite-saturated solutions were also dilute, probably CO 2 -bearing, and were derived from an isotopically distinct source region, possibly one undergoing contact metamorphism (delta 18 O water = 14.8 to 17.0ppm, delta D = -48 to -60ppm). Sphalerite-saturated solutions, in contrast, were brines (8.5 to 12.0 equiv wt % NaCl max, delta D = -30 to -61ppm), which were introduced repeatedly in the early parts of the first three stages of mineralization and were present in the vein structure only briefly. These intermittent brines were the mineralizing fluids responsible for silver and base metal deposition.Helium isotope compositions ( 3 He/ 4 He) measured for inclusion fluids from quartz, calcite, and sulfides (stages I, II, III, and IV) range from 1.1 to 2.1 times the atmospheric ratio (R a ). These values suggest the presence of a dilute component of mantle helium, derived from a subjacent magmatic region at the time of hydrothermal activity. However, helium isotope signatures appear to be completely separated from the other hydrologic factors which governed the chemistry and stable isotope compositions of the distinct hydrothermal fluids.A model for ore genesis is proposed in which metalliferous brine solutions, of magmatic origin, were injected repeatedly and episodically into a hydrothermal system dominated by dilute, quartz-saturated solutions. Metal sulfides and sulfosalts precipitated rapidly under the influence of boiling conditions. Stage IV calcite precipitation marks the end of ore deposition and the influx of fluids from a distinctly different source region.