We use an atmospheric GCM that incorporates stable isotopes and regional vapor source tracers in the hydrologic cycle to explore the relationship between interannual variability in climate and precipitation Δ18O globally. On the basis of a 12-year simulation forced by observed sea surface temperatures (SSTs), we identify changes in the amount of precipitation and in the contributions of local and nearby vapor sources as the most important determinants of simulated interannual isotopic changes. The model simulates weak positive correlation between temperature and isotopic variability only in certain continental regions, mostly in the extratropics. Comparison with long observed records of isotopes and climate indicates that the model simulates realistic patterns of temperature-isotope correlation but may overestimate the isotopic influence of precipitation amount. Perturbations in circulation patterns that alter the transport and mixing of air masses at a site also change the relative contributions of vapor from different source regions. Simulated changes in vapor source regions are large, reaching ¿10--15% of the total precipitation, and cause significant isotopic variability in nearly all grid cells. Our results suggest that shifts among vapor sources may provide an important control on the interannual isotopic variability observed in modern precipitation and paleoclimatic records. The isotopic variability simulated in this experiment results from the interaction of several aspects of climate. Interannual temperature variability generally involves circulation changes that alter air mass transport, vapor source regions, and condensation history; this advective mechanism may explain the relative weakness of temperature-isotope correlations in both the model and the observations. ¿ 1999 American Geophysical Union