To more adequately protect receiving water bodies, government policy is leading toward adaptation of integrated management approaches that protect the integrity of the ecosystem as a whole. Approaching natural water quality is a goal of integrated water resource management. Ecoregions represent geographical areas of relatively similar land surface form, mineral availability, natural vegetation and land uses, and therefore, represent areas of relatively similar background water quality. Water quality at relatively unimpacted reference locations is representative of regional natural water quality and may be reasonably extrapolated to other similar locations within the ecoregion. These concepts were applied to the Southeastern Wisconsin Till Plains ecoregion and the Milwaukee River, Wisconsin.