First measurements of /2O> ratios in the lower mesosphere (50--70 km) are described. HDO and H2O abundances were obtained over the period 1992--2002, by ground-based observation of microwave (λ ~ 1.4 mm) spectral emission lines. Measured HDO depletions are highly variable, with δD values ranging from -58% ¿ 3% to -3% ¿ 9% (58% to 3% less deuterium than standard mean ocean water). Mesospheric δD values decrease with increasing H2O abundance. This is contrary to the stratospheric increase of δD with increasing H2O abundance, indicating that the physical mechanisms controlling mesospheric HDO depletion are fundamentally different from the mechanism (conversion of methane to water) known to control stratospheric HDO depletion. A photochemical model is used to show the observed mesospheric HDO depletion behavior is consistent with slower photolysis of HDO than of H2O. The difference in photolysis rates follows from a difference in cross sections of the two isotopomers at wavelengths >175 nm. Water photolysis in this spectral region is important only in the lower mesosphere. Therefore this mechanism for isotopic separation does not conflict with results of accepted stratospheric studies.