Reinforced concrete (RC) moment frames are the most common form among the building type structures in Turkey. The contemporary seismic design of building type structures evolves around the definition of deviations from an ideal structure that has a square-like floor plan, symmetric and uniform framing and mass distribution. These deviations are called the irregularities which are grouped in two as horizontal and vertical irregularities. There exists a horizontal irregularity that is not addressed in the current approach but it is needed to be investigated due to its possible impact on the lateral stiffness of the structure. It is the discontinuity of the horizontal grid in the structural frame. The purpose of this study is to investigate the earthquake response of the RC buildings that have horizontal grid discontinuities. It is intended to observe the level of additional vulnerability on the seismic response of RC moment frames due to this irregularity. Two 5-story reinforced concrete buildings are modeled in order to investigate the effects of the grid discontinuity phenomenon using nonlinear time-history analysis. The first building has discontinuous beams and framing that demonstrates the irregularity in the plan while the second one is the control case with uniform structural framing. The results are evaluated based on the member damage level. It is observed that the buildings with grid discontinuities are more vulnerable than those without irregularities to seismic excitation. Further study is needed to define a procedure to mitigate the vulnerability created by the horizontal grid discontinuity.