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The variability in delta O-18 and delta O-13 composition of modern and fossil mollusk shells in central-western Argentina was assessed in order to contribute to a better understanding of their value as paleoclimatic indicators. Living mollusks were collected from 17 sites distributed along a latitudinal/altitudinal gradient in Mendoza Province. Quaternary mollusks were obtained from five alluvial successions outcropping in river margins from the same area. Results indicated that delta O-18(shell) reflects the isotope composition of ambient water. For rivers, mollusks reflect the highly depleted isotopic values recorded in the catchment areas (glaciers). Mollusks inhabiting brackish lakes exhibited the maximum enrichment isotope values in coincidence with high evaporation. Variations in delta O-13(shell) were consistent with regional variations in productivity. No differences in delta O-18 and delta O-13 values were recorded among different species coexisting at the same site, suggesting that mollusks exhibit minor, if any, physiological fractionation effects. The high delta O-18 values obtained in Late Pleistocene shells suggest an increased evaporation rate for this moment, in coincidence with the development of damp areas characterized by an increase of ice melting in a warmer phase. An O-18 enrichment together with a C-13 depletion was recorded during the Holocene, suggesting less productive paleoenvironments, probably due to the incidence of more arid conditions than present.