Single photon emission computed tomography (SPECT) imaging with 201Tl or 99mTc agent is used to assess the location or the extent of myocardial infarction or ischemia. A method is proposed to decrease the effect of operator variability in the visual or quantitative interpretation of scintigraphic myocardial perfusion studies. To effect this, the patient's myocardial images (target cases) are registered automatically over a template image, utilizing a nonrigid transformation. The intermediate steps are: 1) Extraction of feature points in both stress and rest three-dimensional (3-D) images. The images are resampled in a polar geometry to detect edge points, which in turn are filtered by the use of a priori constraints. The remaining feature points are assumed to be points on the edges of the left ventricular myocardium. 2) Registration of stress and rest images with a global affine transformation. The matching method is an adaptation of the iterative closest point algorithm. 3) Registration and morphological matching of both stress and rest images on a template using a nonrigid local spline transformation following a global affine transformation. 4) Resampling of both stress and rest images in the geometry of the template. Optimization of the method was performed on a database of 40 pairs of stress and rest images selected to obtain a wide variation of images and abnormalities. Further testing was performed on 250 cases selected from the same database on the basis of the availability of angiographic results and patient stratification.