California's primary hydrologic system, the San Francisco estuary and its upstream watershed, is vulnerable to the regional hydrologic consequences of projected global climate change. Projected temperature anomalies from a global climate model are used to drive a combined model of watershed hydrology and estuarine dynamics. By 2090, a projected temperature increase of 2.1°C results in a loss of about half of the average April snowpack storage, with greatest losses in the northern headwaters. Consequently, spring runoff is reduced by 5.6 km³ (∼20% of historical annual runoff), with associated increases in winter flood peaks. The smaller spring flows yield spring/summer salinity increases of up to 9 psu, with larger increases in wet years.