Abstract We present a novel approach for a combined homogenization and registration technique. Medical image data is often disturbed by in- homogeneities from staining, illumination or attenuation. State-of-the- art approaches tackle homogenization and registration separately. Our new method attacks both troublemakers simultaneously. It is modeled as a minimization problem of a functional consisting of a distance measure and regularizers for the displacement ¯eld and the grayscale correction term. The simultaneous homogenization and registration enables an au- tomatic correction of gray values and improves the local contrast. The combined approach takes slightly more computing time for an optimiza- tion step as compared to the non-combined scheme and so is much faster than sequential methods. We tested the performance both on academic and real life data. It turned out, that the combined approach enhances image quality, especially the visibility of slightly di®erentiable structures.