Intercomparison of atmospheric measurements is often a difficult task because of the different spatial response functions of the experiments considered. We propose a new method for comparison of two atmospheric profiles characterized by averaging kernels with different vertical resolutions. The method minimizes the smoothing error induced by the differences in the averaging kernels by exploiting an optimal interpolation rule to map one profile into the retrieval grid of the other. Compared with the techniques published so far, this method permits one to retain the vertical resolution of the less-resolved profile involved in the intercomparison.