RC frames with masonry infills are a widespread construction form in seismically active regions. Under seismic loading, masonry infills are activated in in-plane direction due to the frame deformation. This leads to the complex frame-infill interaction which can cause the failure of masonry infills or whole RC frame structures. Therefore, the in-plane behaviour of infilled RC frames was a subject of many research projects that aim to predict the seismic performance of infilled frame structures or prevent the damage in masonry infills. Among many parameters that affect seismic response of infilled frames, openings are recognized to play the most significant role as they can affect the stress fields and thus alter the failure mechanism of masonry infills. This paper presents results of the investigation of in-plane behaviour of masonry infilled RC frames with and without openings. In the study, experimental results are firstly presented, and they are afterwards used for validation of numerical model. Further, influence of different opening arrangements on in-plane response of infilled frames is studied in numerical simulations. Results of the study show that openings cause the extensive damage on masonry infills and thus lead to deterioration in in-plane behaviour of infilled RC frames. 2127COMPDYN 2023 9 th ECCOMAS Thematic Conference on Computational Methods in Structural Dynamics and Earthquake Engineering M. Papadrakakis, M. Fragiadakis (eds.