This article uses a basin-wide hydrologic model to assess the hydrologic and economic effects of expanding agriculture in the So Francisco River Basin, Brazil. It then uses a basin-wide economic model of agriculture to examine the effects of implementing water use regulations. Preliminary results suggest that substantially expanding agriculture would put pressure on some of the river's environmental flows. Agricultural output and rural employment would increase, though not in spatially uniform ways. The economic model demonstrates how cropping area, crop mix and production technology respond simultaneously to water shortages. While farmers can adjust, the costs of doing so may be beyond the reach of resource-poor farmers.