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Reinforced concrete (RC) frames with masonry infills are frequently used in seismic regions all over the world. Generally masonry infills are considered as nonstructural elements and thus are typically neglected in the design process. However, the observations made after strong earthquakes have shown that masonry infills can modify the dynamic behavior of the structure significantly. The consequences were total collapses of buildings and loss of human lives. This paper presents the new system INODIS (Innovative Decoupled Infill System) developed within the European research project INSYSME (Innovative Systems for Earthquake Resistant Masonry Enclosures in RC Buildings). INODIS decouples the frame and the masonry infill by means of special U-shaped rubbers placed in between frame and infill. The effectiveness of the system was investigated by means of full scale tests on RC frames with masonry infills subjected to in-plane and out-of-plane loading. Furthermore small specimen tests were conducted to determine material characteristics of the components and the resistances of the connections. Finally, a micromodel was developed to simulate the in-plane behavior of RC frames infilled with AAC blocks with and without installation of the INODIS system.