This article reports a study of modeled, long-period building responses to ground-motion simulations of earthquakes in the San Francisco Bay Area. The earthquakes include the 1989 magnitude 6.9 Loma Prieta earthquake, a magnitude 7.8 simulation of the 1906 San Francisco earthquake, and two hypothetical magnitude 7.8 northern San Andreas fault earthquakes with hypocenters north and south of San Francisco. We use the simulated ground motions to excite nonlinear models of 20-story, steel, welded moment-resisting frame (MRF) buildings. We consider MRF buildings designed with two different strengths and modeled with either ductile or brittle welds. Using peak interstory drift ratio (IDR) as a performance measure, the stiffer, higher strength building models outperform the equivalent more flexible, lower strength designs. The hypothetical magnitude 7.8 earthquake with hypocenter north of San Francisco produces the most severe ground motions. In this simulation, the responses of the more flexible, lower strength building model with brittle welds exceed an IDR of 2.5% (that is, threaten life safety) on 54% of the urban area, compared to 4.6% of the urban area for the stiffer, higher strength building with ductile welds. We also use the simulated ground motions to predict the maximum isolator displacement of base-isolated buildings with linear, single-degree-of-freedom (SDOF) models. For two existing 3-sec isolator systems near San Francisco, the design maximum displacement is 0.5 m, and our simulations predict isolator displacements for this type of system in excess of 0.5 m in many urban areas. This article demonstrates that a large, 1906-like earthquake could cause significant damage to long-period buildings in the San Francisco Bay Area.