In 2002, the Susquehanna River Basin Commission (SRBC) conducted a pilot study to determine appropriate methods for assessing the biology of the large rivers in the Susquehanna River Basin. Based on the results of the pilot study, SRBC determined that a combination of sampling with rock baskets and traditional Rapid Bioassessment Protocol (RBP) methods was the most efficient and consistent collection method to sample the Susquehanna River. Accordingly, SRBC applied the combined methods for the 2005 Susquehanna Large River Assessment Project. Biological and water chemistry data were collected at 25 stations during August through October 2005 on the mainstem Susquehanna River and at the mouths of the three major tributaries: the West Branch Susquehanna River, the Juniata River, and the Chemung River. Ten macroinvertebrate samples were collected at each station, using five rock baskets and five kick nets, when possible. A total of 102 rock basket samples and 125 kick net samples were collected during the survey. Six of the stations were designated moderately impaired, while 19 of the stations were designated slightly impaired. Only 79 out of 950 laboratory and field water quality data points exceeded standards or levels of tolerance for aquatic life, indicating that the Susquehanna River contains fairly good water quality. For future projects, SRBC plans to re-evaluate the need for both rock basket samplers and traditional RBP methods to collect biological data. Staff also will be considering alternative methods for assessing physical habitat and determining ways to assess the reservoir system at the lower end of the Susquehanna River.