This paper will describe the seismic behaviour of masonry infilled RC frame with a central opening structure under reversed cyclic lateral loading. To achieve the purpose of this study, four 1/4-scale single story and single bay RC frame specimens were tested, i.e. one bare frame, one clay brick masonry infilled RC frame without opening and two clay brick masonry infills with a central opening in infills. The ratios of opening size to panel area were 25% and 40%. Through reversed cyclic lateral loading tests, the seismic performance of RC frames with a central opening brick masonry infills was investigated. As the results, significant distinctions of failure mechanism, lateral strength, stiffness, and ductility were observed between these specimens. In the case of infills with a central opening, the cracks sprouted and developed at the corners of the opening. Although the presence of the opening in infill reduces the lateral strength and stiffness overall structure, the brick infilled frames with a central opening of 25% and 40% of panel area show better seismic performance as compared to the bare frame.