New algorithms for automated comparison of scintigraphic images have been developed and are described here. The first step presented here is the registration of the images, performed by optimizing, with respect to the registration parameters (two translational shifts, one angle of rotation, the two parameters of a linear transformation of the gray levels), the stochastic sign change (SSC) criterion. The optimization of this criterion is demonstrated to be efficiently performed using the adaptative random search strategy; a more limited but less time-consuming method is also presented. The second step described is the point-by-point comparison of the registered images. The pixel-by-pixel application of Poisson variable statistical tests permits the generation of the significant image differences. From such images it is possible to detect modifications which escape visual inspection. Examples of applications are given in controlled and routine conditions. These algorithms are useful for the processing of many investigations and are proposed for implementation on all nuclear medicine data processing systems.