Within the INSYSME Project, funded under the 7th Framework Program by the Commission of the European Communities and aimed at developing innovative systems for masonry enclosure walls, the University of Padova and ANDIL (Italian Association of Clay Bricks and Roofing Tiles Producers) proposed a construction system named DRES (Damage Reduction Enclosure System). The system is made of a single-leaf clay masonry wall, with three horizontal deformable joints within the clay unit rows, to be employed in RC frame buildings in regions prone to medium/high intensity earthquakes. To understand the behaviour of this system, an experimental campaign on four real-scale, one-bay, one-storey RC frames infilled with both partial and full enclosure walls, was performed. The tests combine cyclic in-plane and monotonic out-of-plane loading of the specimen. Two variants of the DRES system and a reference plain masonry enclosure were first tested in the in-plane direction and then in the out-of-plane direction. An additional specimen infilled with two partial enclosures, one built with DRES and one with plain masonry, was first tested in the out-of-plane direction and then, after removal of damaged walls from the bare frame, tested in the in-plane direction. An analysis, in terms of strength, ductility parameters and damage, of the in-plane and the out-of-plane test results is carried out.