The current (1996–1997 survey) mammalian fauna of the Cuatro Ciénegas Basin, Coahuila, Mexico, is compared with records of the past century as well as records from undated (pre-1953) owl-pellet records and undated (pre-1700) archaeological remains. The basin supports one of the largest freshwater areas in the deserts of northern Mexico and is located along the Sierra del Carmen–Sierra Madre Oriental Filter-Barrier, between the arid Chihuahuan and tropical Tamaulipan biotic provinces. The freshwater environment has remained remarkably stable through Pleistocene climatic oscillations, but more recently has been subjected to human-induced impact. Comparison of archaeological, historical, and current mammalian fauna depicts the well-known extirpation of larger carnivores and ungulates by humans; the shift to a drier, more Chihuahuan environment; and loss of species during the past century, including the apparent and unexplained disappearance of 4 species of rodents from the basin.