The estimation of regional risks due to multiple Stressors is a frontier in environmental toxicology and risk assessment. We are conducting a regional scale ecological risk assessment of multiple Stressors in the Willamette Valley, Oregon. The Willamette River drains an extensive agricultural area and forests of both the Coastal and Cascades mountains. The river also receives effluents from paper mills and urban wastewater treatment facilities. A major tributary of the Willamette is the McKenzie River. The McKenzie watershed, which extends into the Cascade Mountains, is extensively forested. Stressors in this watershed include alterations in the landscape due to the harvest of trees, the infrastructure required for the logging, modification of the river or stream banks, and inputs due to contamination by localized urban and non-point sources. We are using the relative risk model (RRM) for ecological risk assessment developed by Wiegers, Landis, and colleagues to combine multiple Stressors and receptors in a regional context. The first step in the RRM process is the establishment of assessment endpoints for the particular area and the placement of the endpoints in the landscape. Next, the method involves the development of risk matrices that combine diverse Stressors and habitats within the region with numerical ranks. We have broken the McKenzie and Willamette watershed study areas into 13 risk regions and have mapped the locations of the point sources and are incorporating land use data. Using a variety of documents we have established the assessment space and are developing criteria for ranking Stressors and habitats. We have also initiated a 3-year field research activity to confirm the risk predictions within the main channel. The sampling sites correspond to the risk regions of the RRM. The sampling program will characterize the population density and structure of the fish assemblage and measuring the health of the individual fish.