We present new major and trace elements and Sr, Nd, Pb, and O isotopic data on basaltic andesite to rhyolitic volcanic rocks from surface outcrops as well as drill wells from the Los Azufres geothermal field (LAGF). With a total installed capacity for electricity production of about 100 MW, LAGF is the second most important geothermal field in Mexico. Hydrothermal alteration has affected most subsurface (drill well) rocks, ranging from partial to complete alteration. The alteration mineralogy with increasing depth (and temperature) is: argillitization/silicification, zeolite/calcite formation, sericitization/chloritization, chloritization/epidotization. The Sr, Nd and Pb isotopic ratios from the LAGF show the following ranges: for surface rocks (Sr-87/Sr-86)(i) approximate to 0.70344-0.7048; (Nd-143/Nd-144)(i) approximate to 0.512745-0.512908; Pb-206/Pb-104 approximate to 18.695-18.725; Pb-207/Pb-204 approximate to 15.585-15.612; Pb-208/Pb-201 approximate to 38.406-38.522; whereas for drill well rocks (Sr-87/Sr-86)(i) approximate to 0.70374-0.70462; (Nd-143/Nd-144)(i) approximate to 0.512675-0.512862; Pb-206/Ph-204 approximate to 18.643-18.770; Pb-207/Pb-204 approximate to 15.590-15.621; Pb-208/Pb-204 approximate to 38.390-38.595. An objective statistical methodology, based on F-ratio and Student-t tests, used for the comparison of chemistry of surface fresh rocks (from the LAGF and the surrounding area), to that of shallow (<1000 m depth) drill well altered rocks reveals that hydrothermal alteration causes a loss of total alkalis in most rock types. High-field strength elements such as Zr, TiO2, and P2O5, generally considered as immobile elements, also show significant hydrothermal alteration-related changes. Finally, Pb isotopic ratios of drill well altered rocks significantly decrease and Nd-143/Nd-144 significantly increase with increasing SiO2. Such a trend of decreasing Pb isotopic ratios and increasing Nd-143/Nd-144 is also observed for hydrothermally-altered rhyolites as compared to fresh rhyolites.