Abstract. A one-dimensional chemistry model is applied to study the stable hydrogen (D) and stable oxygen isotope (¹⁷O, ¹⁸O) composition of water vapour in stratosphere and mesosphere. In the troposphere, this isotope composition is determined by "physical'' fractionation effects, that are phase changes (e.g. during cloud formation), diffusion processes (e.g. during evaporation from the ocean), and mixing of air masses. Due to these processes water vapour entering the stratosphere first shows isotope depletions in D/H relative to ocean water, which are ~5 times of those in ¹⁸O/¹⁶O, and secondly is mass-dependently fractionated (MDF), i.e. changes in the isotope ratio ¹⁷O/¹⁶O are ~0.52 times of those of ¹⁸O/¹⁶O. In contrast, in the stratosphere and mesosphere "chemical'' fractionation mechanisms, that are the production of H_O due to the oxidation of methane, re-cycling of H₂O via the HO_x family, and isotope exchange reactions considerably enhance the isotope ratios in the water vapour imported from the troposphere. The model reasonably predicts overall enhancements of the stable isotope ratios in H₂O by up to ~25% for D/H, ~8.5% for ¹⁷O/¹⁶O, and ~14% for ¹⁸O/¹⁶O in the mesosphere relative to the tropopause values. The ¹⁷O/¹⁶O and ¹⁸O/¹⁶O ratios in H₂O are shown to be a measure of the relative fractions of HO_x that receive the O atom either from the reservoirs O₂ or O₃. Throughout the middle atmosphere, MDF O₂ is the major donator of oxygen atoms incorporated in OH and HO₂ and thus in H₂O. In the stratosphere the known mass-independent fractionation (MIF) signal in O₃ is in a first step transferred to the NO_x family and only in a second step to HO_x and H₂O. In contrast to CO₂, O(¹D) only plays a minor role in this MIF transfer. The major uncertainty in our calculation arises from poorly quantified isotope exchange reaction rate coefficients and kinetic isotope fractionation factors.