Several designs of future Adaptive Optics (AO) systems propose to use a large Deformable Mirror (DM), regarding the size as well as the number of actuators. Most of the time, there is no focal plane upstream the DM. Therefore, the classical way of calibrating the interaction matrix on an artificial source cannot be applied. Furthermore, the requirements in terms of calibration error budget are tight and the high order modes of such DMs are stiff and hence they achieve only a small stroke. This is why novel ways to determine the system Interaction Matrix (IM) have to be investigated. Several paths have been studied. One solution would be to simulate a synthetic IM. However, calibration on sky is also an option. Different techniques were simulated, tested and optimized on real AO systems. The results are presented in this paper.© (2006) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.