Infill walls are generally not taken into account in structural analysis due to their complex behavior at seismic actions. As it is known, they increase the stiffness as well as the lateral load capacity of the system. Sometimes, infill walls may have window and door openings in their planes. In the present study, behavior of reinforced concrete (RC) frames with infill wall which have openings is investigated under cyclic lateral loadings. Location and size of the openings in the infill wall are selected as investigation parameters. Test specimens are constructed and experimentally analyzed. The infill wall changes the behavior of the frames under cyclic lateral loads significantly. Location and size openings in the infill wall are two main parameters which affect the behavior of the infill walls as well as on that of the frame. The test results clearly show that the contribution of the infill wall to the behavior of RC frame has diminished significantly when the opening ratio is larger than 9%. Therefore, the effect of the opening in the infill wall must be taken into account in the structural modeling when the opening ratio is larger than 9%.