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The combination of multiple satellite instruments on a pixel-by-pixel basis is a difficult task, even for instruments collocated in space and time, such as the Moderate Resolution Imaging Spectroradiometer (MODIS) and Atmospheric Infrared Sounder (AIRS) on board the Earth Observing System (EOS) Aqua. Toward the goal of an improved collocation methodology, the channel- and scan angle–dependent spatial response functions of AIRS that were obtained from prelaunch measurements and calculated impacts from scan geometry are shown within the context of radiance comparisons. The AIRS spatial response functions are used to improve the averaging of MODIS radiances to the AIRS footprint, and the variability of brightness temperature differences (Δ Tb) between MODIS and AIRS are quantified on a channel-by-channel basis. To test possible connections between Δ Tb and the derived level 2 (L2) datasets, cloud characteristics derived from MODIS are used to highlight correlations between these quantities and Δ Tb, especially for ice clouds in H2O and CO2 bands. Furthermore, correlations are quantified for temperature lapse rate ( dT/ dp) and the magnitude of water vapor mixing ratio ( q) obtained from AIRS L2 retrievals. Larger values of dT/ dp and q correlate well to larger values of Δ Tb in the H2O and CO2 bands. These correlations were largely eliminated or reduced after the MODIS spectral response functions were shifted by recommended values. While this investigation shows that the AIRS spatial response functions are necessary to reduce the variability and skewness of Δ Tb within heterogeneous scenes, improved knowledge about MODIS spectral response functions is necessary to reduce biases in Δ Tb. [ABSTRACT FROM AUTHOR]