The lateral loads imposed on a building structure by a major earthquake may, at times, produce an overturning moment that equals or exceeds the available overturning resistance provided by gravity loads. In such a case, unless the foundation has been adequately anchored to the underlying rock or soil, parts of it may experience a transient uplift causing the building to rock about its foundation. Uplift is expected to reduce the level of seismic response of structures. Such beneficial effect has been observed during past earthquakes in a limited number of cases. The present study is related to the response of steel framed buildings founded on spread footings and subjected to recorded earthquakes. The study is aimed at examining the effect of important system parameters on the uplift response. These parameters include: the slenderness ratio of the building, the magnitude of live load, the vertical component of earthquake motion, type of framing (simple or rigid joints), and the flexibility of the underlying soil. The results of the study show that rigid frame steel buildings with practical levels of live load to dead load ratio are unlikely to uplift even under severe earthquakes. Braced frames, on the other hand, do have a tendency to uplift. The results show that in braced frames, uplift, in general, reduces the base shear and column axial forces. However, the effect on the lateral displacements is not always beneficial. Depending on the characteristics of the building and the earthquake, uplift may either reduce or increase the displacements.