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Many reinforced concrete buildings have been built with masonry infill walls for architectural needs without considering their mechanical contribution. However, ignoring the structural influence of infills may lead to significant inaccuracies in the prediction of the actual seismic capabilities of the structure. Aiming at providing numerical tools suitable for engineering practice, simplified methodologies for predicting the nonlinear seismic behaviour of infilled frame structures (IFS) have been proposed, mostly considering the contribution of the infill as an equivalent diagonal strut element. In this paper, an alternative plane macro-element approach for the seismic assessment of IFS is proposed, validated and applied to a benchmark prototype building. The model validation is focused on recent experimental and numerical results that investigate the influence of non-structural infills, also in the presence of different openings layouts. As a benchmark investigation, a multi-storey plane frame prototype, for which the results of pseudo-dynamic tests are available, is investigated and compared to the results obtained by using a commonly adopted single-strut model. The merits and drawbacks of the considered numerical approaches are highlighted.