Deep phreatic shafts and travertine-capped sinkholes characterize Sistema Zacatón, an isolated karst area in northeastern Mexico. At a depth of at least 329 m, El Zacatón is the deepest known underwater pit in the world. Hypogenic karst development related to volcanism is proposed to have formed El Zacatón and is thought to have diminished since the late Quaternary peak activity. The resulting geomorphic overprint of Zacatón displays features similar to hydrothermal groundwater systems throughout the world. Other karst areas in northeastern Mexico are known for deep pits and high-flow springs rising from great depths, but differ from Zacatón in the speleogenetic processes that developed the caves. Sótano de Las Golondrinas (378 m), 200 km to the southwest of Zacatón, is among the deepest air-filled shafts in the world. The Nacimiento del Río Mante, 100 km to the west, is a large artesian spring that extends a minimum of 270 m below the water table. Although these three world-class karst systems all formed in Cretaceous limestone and are located relatively close together, there are significant differences in lithology, tectonic setting, and geomorphic features. Geochemical, microbiological, and geomorphologic data for Zacatón indicate that cave formation processes are similar to those observed in other volcanically influenced systems.