In this paper a recently presented tuning technique for multiple-input multiple-output (MIMO) systems (Loh et d., 1993), which avoids a trial and error approach; is analysed into detail to understand to what systems it can be extended and in which cases it can be unsuccessful. The technique, which is based on sequential and (if it is the case) iterative autotuning of PI controllers using relay feedback, is shown to be applicable also to the control of MIMO systems with negative values of the relative gain array (RGA) and to systems with inner cascade loops. Moreover controllers for MIMO open-loop unstable systems, which are stabilizable by conventional controllers, can be tuned combining the multiloop autotuning with a recently developed autotuning technique for single-input single-output unstable systems (Semino and Gori, 1995). On the other side, it is shown that for some MIMO open-loop stable systems the tuning procedure can be successful only if an ad-hoc refinement of the Ziegler-Nichols tuning method is adopted.