Abstract. Over the last five years, new "voxel-based" approaches have allowed important progress in multimodal image registration, notably due to the increasing use of information-theoretic similarity measures. Their wide success has led to the progressive abandon of measures using standard image statistics (mean and variance). Until now, such measures have essentially been based on heuristics. In this paper, we address the determination of a new measure based on standard statistics from a theoretical point of view. We show that it naturally leads to a known concept of probability theory, the correlation ratio. In our derivation, we take as the hypothesis the functional dependence between the image intensities. Although such a hypothesis is not as general as possible, it enables us to model the image smoothness prior very easily. We also demonstrate results of multimodal rigid registration involving Magnetic Resonance (MR.), Computed Tomography (CT), and Positron Emission Tomography (PET) images. These results suggest that the correlation ratio provides a good trade-off between accuracy and robustness.