In-filled masonry panels are commonly used as partitions in low-rise RC buildings. When the masonry panels are perforated with door or window openings, the structural behavior become complicated and difficult to be analyzed. This paper presents the results of lateral load experiments on in-filled masonry panels with openings in RC frames. Two full-sized specimens were tested under constant vertical force and displacement-controlled cyclic in-plane lateral load. The specimens included an RC frame with a door opening on the in-filled masonry panel and the bare frame with the panel demolished after the first test. The test results show that the panel-frame interfaces cracked soon after the loading started. As the displacement increased, the panel and the columns tended to deform independently. The masonry panel had bed-joint sliding failure, while the columns were only cracked with double-curvature bending behavior in the end of the test. The columns in the bare frame test showed flexural failure prior to ductile shear failure. A comparison between the two tests indicates that the panel provided partial restraint to the column deformation but did not change the failure mode of the frame. Analytical capacity curve by using the FEMA356 model for in-filled masonry panel without opening are compared with the experimental curve. Modifications for the analytical model are presented.