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Spatial and temporal variability in stable isotopic compositions (delta O-18 and delta D) in river water of the Yarlungzangbo was investigated to identify major hydrological processes along the river channel and evaluate the isotopic response to discharge variation. The results show geographic, distinct isotopic evolutions in the Yarlungzangbo system. Along the main stem, river delta O-18 exhibits a decreasing trend from the headwaters to the middle reach but an increasing one from the middle to the lower reaches, and main flows demonstrate much greater delta O-18-dD slope and intercept compared to the global meteoric water line (GMWL) and reported local meteoric water lines (LMWLs) for sites within the basin. These results are found to be consistent with the isotopic characteristics of stream and river waters collected across the entire drainage basin. Water mixing appears to be the dominant hydrological process along the Yarlungzangbo, and the pattern of isotopic change in individual river reaches closely reflects that of precipitation in corresponding part of the river basin. The isotopic variability along the main stem observed during the synoptic survey is evidenced to hold through time by a time-series investigation at three key hydrological stations. River water at such three stations shows a strong isotopic response to discharge variability. In general, river delta O-18 tends to be negatively correlated with discharge, highlighting a typical monsoon precipitation-driven isotope-discharge pattern. Specifically, we found their individual discharge-weighted average delta O-18 values likely vary in a similar rate with the ratio of mean discharge in monsoon season (JAS) to that in pre-monsoon season (MJ) on a yearly basis, indicating a specific relationship between average river isotopic composition and discharge seasonality throughout their drainage areas (i.e. the middle-lower Yarlungzangbo basin). This study thus demonstrates the usefulness of isotopic data for assessing hydrodynamics over a less explored, complex and high-altitude large river catchment. (c) 2017 Elsevier B.V. All rights reserved.