The Andean mountain range has played an important role in the evolution of South American biota. However, there is little understanding of the patterns of species diversity across latitudinal and altitudinal gradients. In this paper, we examine the diversity of small mammals along the South Central Dry Andes (SCDA) within the framework of two contrasting hypotheses: (a) species richness decreases with increasing elevation and latitude; and (b) species richness peaks at altitudinal midpoints (mid-domain). We explore the composition of the species pool, the impact of species–area relationships and the Rapoport effect (i.e. size of geographic ranges) along latitudinal and elevational gradients. First, we constructed a database of SCDA small mammals. Then, species richness patterns were analysed through generalized models, and species–area relationships were assessed by log–log regressions; the curvilinear method (c = S/Az) was use to compute richness corrected by area size. Lastly, the Rapoport effect was evaluated using the midpoint method. Our results show: (1) a richness of 67 small mammals along the SCDA, of which 36 are endemic; (2) a hump-shaped pattern in species richness along elevation and latitudinal gradients; (3) a species–area relationship for both gradients; (4) endemic species corrected by area present a strong and positive relationship with elevation; (5) a Rapoport effect for the latitudinal ranges, but no effect across the elevational gradient; and (6) a major species turnover between 28° and 30° south latitude. This is the first study quantifying the diversity of small mammals encompassing the central Andean region. Overall, our macrogeographic analysis supports the previously postulated role of the Andes in the diversification of small mammals (i.e. in situ cladogenesis) and highlights some basic attributes (i.e. anatomy of geographic ranges; species–area relationships) when considering the consequences of climate change on biodiversity conservation of mountain ecosystems.