The Agave genus embraces many species with outstanding ecological and economic importance in the arid regions of the Americas. Even though this genus covers a broad geographic distribution, our knowledge on the population genetics of species is concentrated in taxa located in North America. Recently, it has been demonstrated that plant domestication decreases levels of genetic diversity in managed populations and increases population structure with respect to wild populations. We examined levels of allozyme diversity (N = 17 loci) and population structure of Agave cocui, the species at the southern limit of distribution of the genus. We sampled 7 wild populations (N = 30-35 individuals per population) representative of the geographic distribution of the species in Venezuela. Among the agaves studied, A. cocui has some of the lowest estimates of genetic diversity (H(e)[species] = 0.059, H(e)[population] = 0.054) reported until present. We propose that this condition is probably linked to the recent origin of this species in arid and semiarid regions of Colombia and Venezuela, probably through one or a few founder events. The lowest estimates of genetic diversity were associated with small populations in very restricted arid patches; but also with overexploitation of rosettes for production of fermented drinks and fibers. Santa Cruz de Pecaya, one of the 2 centers of economic use of agaves in northwestern Venezuela presented one of the lowest values of genetic variability, a sign suggesting that human impact represents a significant threat to the available genetic pool that this species possesses in the region.