Varying ages from Triassic to Pliocene have been proposed for the onset of hyperaridity in the Atacama Desert. The exact timing for the initiation of hyperaridity is critical for determining potential causes, which range from regional effects of global cooling to Andean uplift above elevations conducive to extreme rain shadows. Analysis of the stable isotopic composition of lower Miocene-Quaternary (21-0.015 Ma) palustrine and lacustrine carbonates in the Calama Basin reveals extreme changes in their oxygen and carbon isotopic composition during the Miocene. Limestone delta O-18 values increased by similar to 5 parts per thousand from middle to late Miocene, ranging from -5.5 parts per thousand at 12 Ma to 1 parts per thousand at similar to 6 Ma. Carbon isotopic values increase by 9 parts per thousand over the Neogene, from average values of -3 parts per thousand at 21 Ma to +3 parts per thousand at 12 Ma, and reaching a maximum of +6 parts per thousand at 5 Ma. The increase in oxygen isotopic values occurred over a time span in which the catchment area of the basin experienced significant uplift, causing the delta O-18 value of precipitation to become more negative. We attribute the shift towards higher delta O-18 values to enhanced evaporative enrichment both of soil water or snow prior to infiltration, and within shallow lakes or wetlands prior to carbonate precipitation. The large increase in delta C-13 values was likely caused by a transition from a vegetated landscape influenced primarily by soil-respired CO2 to a landscape largely devoid of vegetation and influenced by atmospheric and volcanic CO2. Isotopic values of palustrine carbonates therefore indicate that hyperaridity commenced in the Calama Basin during the middle to late Miocene, in agreement with other paleoclimatic records from the basin. The cause for the onset of this climate change is thought to be clue to the development of a strong Andean rain shadow associated with the uplift of the Andes to mean elevations >2 km. (C) 2010 Elsevier B.V. All rights reserved.