In the seismic response analysis of large structures the effects of differential support excitation should be considered. The differential support excitation may be due to asynchrony in excitation of different supports, caused by the finite speed of traveling earthquake waves and/or due to non-uniformity of these excitations, resulting from a change in the properties of the earthquake waves as they travel. In this paper; due attention is given to the question of non-uniformity of support excitation and its effects on the response of such structures as gravity dams and cluster buildings. Non-uniformity of ground excitation is modeled using a set of simulated acceleration time histories obtained from a representative spatial variability model. Comparative studies on the effects of asynchrony and non-uniformity of supports motion on the structural response show that non-uniformity may, in some cases, amplify the effects of asynchrony and therefore should be considered in the analysis. It is also shown that for cluster buildings and buildings with large floor areas, the effects of differential support excitation could be considerable.