The Los Azufres caldera (Michoacán, Mexico) is located in the Trans-Mexican Volcanic Belt (MVB). The pre-caldera volcanic basement consists of a 3-km-thick pile of andesitic flows, intruded and/or overlain by rhyolitic and dacitic domes and flows. The geochemistry of the volcanic layers has been investigated in three deep wells (A9, A25 and A48) down to 3.0 km. Such deep wells have given the opportunity to investigate the geochemical changes related to the hydrothermal metamorphism as well as the stratigraphy of the thick volcanic pile.Systematic analysis of major elements in cores and cuttings shows that the partial to total hydrothermal metamorphism of the series from the greenschist to the amphibolite facies produces significant geochemical changes on the whole-rock geochemistry. Gains in CO2, H2O and depletions in alkalis are especially observed and may be related with the crystallization of carbonates and phyllosilicates. However, the depth-concentration profiles have shown that most other elements (such as Al, Fe, Ca, Mg, P and Ti) display moderate changes due to hydrothermal alteration in comparison with their initial variations of magmatic origin. Rythmic compositional changes are observed all along the volcanic pile, with progressive changes in rock composition from basalts to dacites within four megasequences of a few hundred meters thickness. Elements rather immobile under hydrothermal conditions, such as Ti, have been especially useful for the reconstruction of magmatic sequence stratigraphy. Variations of element concentrations seem mostly due to magmatic differentiation of parental basalts which produces compositions from basaltic andesites to dacites. However, the four magmatic suites distinguished display calc-alkaline features coherent with other suites of the MVB volcanoes.