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Analyses and results of the radiometric calibration accuracy and measurement characteristics of the first Defense Meteorological Satellite Program (DMSP)'s Special Sensor Microwave Imager/Sounder (SSMIS) upper atmosphere sounding (UAS) channels are presented herein. Launched on October 18, 2003, aboard the DMSP F-16 spacecraft in a sun-synchronous orbit, the SSMIS UAS channels provide the first operational measurements of microwave radiation emitted by the Earth's atmosphere at mesospheric altitudes. The analysis of the SSMIS radiometer absolute calibration and stability is based upon extensive comparisons with a fully polarimetric radiative transfer model (RTM) that solves for all four Stokes parameters using coincident atmospheric temperature profiles derived from collocated Rayleigh lidar observations merged with the European Centre for Medium-Range Weather Forecasting temperature analyses and climatological data sets. The resulting merged profiles provide a physically consistent temperature profile from the surface to 100 km, as needed by the RTMs. The results presented herein of the SSMIS instrument show that significant hardware and scientific technical challenges arise from microwave temperature sounding of the mesosphere. These include the following: 1) addressing the impact of large noise-equivalent temperature difference associated with narrow channel bandwidths; 2) achieving high channel center-frequency stability; 3) compensation of large spacecraft-induced Doppler shift; 4) better characterization of the Zeeman splitting of the oxygen absorption lines; 5) development of a fast polarimetric RTM; and 6) designing stable and accurate on-orbit radiometric calibration targets. Results to date show that the uncertainties of the calibration accuracy of the SSMIS UAS channels are consistent and in agreement with the limits derived for the SSMIS UAS channels and with the simulated radiances derived from the merged lidar profiles.