Major bridges in areas of high seismicity are often supported on deep pile foundations. During an earthquake, ground shaking is not uniform in the entire soil domain supporting a bridge and its foundations. Ground motions may be different at each support and at various depths along each pile. In particular, site response effects alter the seismic waves as they propagate upward, leading to depth-varying motions. This raises the question of what motions are the most appropriate for use in evaluating the seismic response of a pile-supported bridge. In this study, excitations caused by depth-varying motions are investigated by performing analysis of kinematic pile-soil interaction. Depth-varying free field motions are computed along the length of the piles and used as inputs through soil springs into foundation models. The resulting "kinematic motion" is computed at the pile cap, which gives an indication of the effective earthquake excitation imparted to the bridge. Results are presented from major bridge projects covering a range of pile types and ground conditions. In terms of their computed response spectra, the kinematic motions are often found to be lower than the free field ground motions at the mudline or ground surface. As a result, seismic design demands may be reduced by implementing kinematic or depth-varying motions in global bridge model analysis, as opposed to following the ground surface response spectrum approach used in standard practice. Significant reductions in demands are found particularly for bridges on stiff pile foundations at sites with soft upper soils underlain by denser materials.