Abstract: The purpose of this special report is to provide a statistical stepwise process for formulation of ecological models for application at multiple scales using a stream condition index (SCI). Given the global variability of aquatic ecosystems, this guidance is for broad application and may require modification to suit specific watersheds or stream reaches. However, the general statistical treatise provided herein applies across physiographies and at multiple scales. The Duck River Watershed Assessment in Tennessee was used, in part, to develop and test this multiscale, statistical approach; thus, it is considered a case example and referenced throughout this report. The findings of this study can be utilized to (1) prioritize water-sheds for restoration, enhancement, and conservation; (2) plan and conduct site-specific, intensive ecosystem studies; and (3) assess ecosystem outcomes (that is, ecological lift) applicable to future with and without restoration actions including alternative, feasibility, and cost-benefit analyses and adaptive management.