The effect of viscous damping and yielding, on the reduction of the seismic responses of steel buildings modeled as three-dimensional (3D) complex multidegree of freedom (MDOF) systems, is studied. The reduction produced by damping may be larger or smaller than that of yielding. This reduction can significantly vary from one structural idealization to another and is smaller for global than for local response parameters, which in turn depends on the particular local response parameter. The uncertainty in the estimation is significantly larger for local response parameter and decreases as damping increases. The results show the limitations of the commonly used static equivalent lateral force procedure where local and global response parameters are reduced in the same proportion. It is concluded that estimating the effect of damping and yielding on the seismic response of steel buildings by using simplified models may be a very crude approximation. Moreover, the effect of yielding should be explicitly calculated by using complex 3D MDOF models instead of estimating it in terms of equivalent viscous damping. The findings of this paper are for the particular models used in the study. Much more research is needed to reach more general conclusions.