In 1857 a large earthquake of magnitude 7.9 (Sieh 1978b) occurred on the San Andreas fault with rupture initiating at Parkfield in Central California and propagating in a southeasterly direction over a distance of more than 360 km. Such a unilateral rupture produces significant directivity toward the San Fernando and Los Angeles basins. Indeed, newspaper reports (Agnew and Sieh 1978; Meltzner and Wald 1998) of sloshing observed in the Los Angeles river point to long-duration (1.2 min) and long-period (2.8 s) shaking, which could have a severe impact on present-day tall buildings, especially in the mid-height range. Using state-of-the-art computational tools in seismology and structural engineering, validated using data from the Northridge earthquake, we determine the damage in 18-story steel moment-frame buildings in southern California due to ground motion from a hypothetical magnitude 7.9 earthquake on the San Andreas fault. Our study indicates that serious damage occurs in these buildings at many locations in the region, leading to wide-spread building closures and seriously affecting the regional economy.