Studying Venus’s HDO and H2O sheds light on its water history. The HDO/H2O ratio in its bulk atmosphere, 120 times Earth’s, suggests a significantly wetter past for Venus. Our study analyzes mesospheric (70 to 110 km) temperature, H2O, and HDO profiles taken in solar occultation by SOIR/Venus Express. We observe increasing relative abundances of both isotopologues and a significant D/H ratio rise with altitude. This finding challenges previous assumptions about upper-mesosphere H and D abundances available for escape, impacting atmospheric evolution models. We propose a cycle mechanism involving water fractionation during condensation into the sulfur-based aerosols, evaporation, and transport in the mesosphere between warm and cold regions to explain our finding, which is consistent with the observed SO2 inversion layer. This study analyzes H2O and HDO vertical profiles in the Venus mesosphere using Venus Express/Solar Occultation in the InfraRed data. The findings show increasing H2O and HDO volume mixing ratios with altitude, with the D/H ratio rising significantly from 0.025 at ~70 km to 0.24 at ~108 km. This indicates an increase from 162 to 1,519 times the Earth’s ratio within 40 km. The study explores two hypotheses for these results: isotopic fractionation from photolysis of H2O over HDO or from phase change processes. The latter, involving condensation and evaporation of sulfuric acid aerosols, as suggested by previous authors [X. Zhang et al., Nat. Geosci. 3, 834–837 (2010)], aligns more closely with the rapid changes observed. Vertical transport computations for H2O, HDO, and aerosols show water vapor downwelling and aerosols upwelling. We propose a mechanism where aerosols form in the lower mesosphere due to temperatures below the water condensation threshold, leading to deuterium-enriched aerosols. These aerosols ascend, evaporate at higher temperatures, and release more HDO than H2O, which are then transported downward. Moreover, this cycle may explain the SO2 increase in the upper mesosphere observed above 80 km. The study highlights two crucial implications. First, altitude variation is critical to determining the Venus deuterium and hydrogen reservoirs. Second, the altitude-dependent increase of the D/H ratio affects H and D escape rates. The photolysis of H2O and HDO at higher altitudes releases more D, influencing long-term D/H evolution. These findings suggest that evolutionary models should incorporate altitude-dependent processes for accurate D/H fractionation predictions.