The aim of factor analysis of medical image sequences (FAMIS) is to estimate a limited number of physical or physiological fundamental functions. Its oblique rotation stage strongly affects the quality and the interpretation of the resulting estimates (factors and factor images). A new target apex-seeking method which integrates physical or physiological knowledge in this stage is described. This knowledge concerns some of the fundamental functions and reacts on the determination of all the factors. A simulated spectral study illustrates the method. We discuss its properties in comparison with the other approaches using a priori physical or physiological information.