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The timing and magnitude of surface uplift provide important constraints on geodynamic models of orogen formation. Oxygen isotope (delta O-18) and mass-47 isotopolog (Delta(47)) compositions from terrestrial carbonate sediments have been used with modern isotope and temperature lapse rates to infer past surface elevations of the Andes. However, these paleoaltimeny interpretations are contentious because variations in the oxygen isotope composition in meteoric water (delta O-18(p)) are caused by changes in elevation (orographic) and regional climate. Here, we use a limited-domain isotope-tracking general circulation model to simulate changes in delta O-18(p) and isotopic lapse rates in response to Andean surface uplift, and to re-evaluate delta O-18 and Delta(47) changes in late Miocene carbonates previously associated with rapid Andean growth. Results indicate that Andean surface uplift leads to changes in low-level atmospheric circulation and an increase in precipitation along the eastem Andean flank which influences isotopic source and amount effects. Simulated changes in Andean delta O-18(p) are not systematic with an increase in surface elevation, but are instead a function of orographic thresholds that abruptly change regional climate. A delta O-18(p) decrease of >5%. over the central Andes and an increase in isotopic lapse rates (up to 0.8%. km(-1)) coincide with Andean surface uplift from 75 to 100% of modem elevation. These changes in the isotopic signature could account for the entire 3-4%. delta O-18 depletion in late Miocene carbonate nodules, and suggest an Andean paleoelevation of similar to 3000 m (75% of modem elevations) before 10 Ma. (C) 2011 Elsevier B.V. All rights reserved.