We show measurements of middle atmospheric water vapor as measured by two ground-based Water Vapor Millimeter-wave Spectrometer instruments and three satellite-based instruments: the Aura Microwave Limb Sounder, the Atmospheric Chemistry Experiment (ACE), and the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS). We also show CH4 measurements from the MIPAS and ACE instruments and use these to help interpret the H2O variations. We find that interannual changes in stratospheric H2O of ~0.5 ppmv, observed from Table Mountain, California, at 26 km and 40 km from 2010 to 2012, are caused primarily by dynamically driven changes in CH4 during this period. The interannual variations in H2O observed over Mauna Loa, Hawaii, are shown to be quite similar to the average variations observed over 50°S–50°N in the lower mesosphere; thus, we conclude that a single ground-based microwave instrument can provide a useful estimate of interannual globally averaged lower mesospheric H2O variations, even when such changes are as small as ~0.2–0.3 ppmv. We find that the increase of ~0.2–0.3 ppmv in H2O in the lower mesosphere since 2006 is qualitatively consistent with an increase in tropical tropopause temperature since around 2001.