Despite their importance, rigorous process models are rarely available for reaction and especially multi-phase reaction systems. The high complexity of these systems, which is due to the superposed effects of mass transfer and intrinsic reaction, is the major barrier for the development of process models. A methodology that allows the systematic decomposition of mass transfer and chemical reaction and thus enables the efficient identification of multi-phase reaction systems is proposed in this work. The method is based on the so-called Incremental Identification Method, recently presented by Brendel et al., Chem Eng Sci. 2006;61:5404-5420. The method allows to easily test the identifiability of a system based on the available measurement data. If identifiability is given, the intrinsic reaction kinetics can be identified in a sound and numerically robust manner. These benefits are illustrated using a simulated 2-phase enzyme reaction system. (C) 2009 American Institute of Chemical Engineers AIChE J, 55: 1009-1022, 2009