Qualitative and quantitative sampling was conducted along a 165 km reach of the river from PRKM 269.4 near Dryden, VA to PRKM 104.8 near Harrogate, TN. Twenty-nine species were observed throughout the entire river, and the highest diversity of 23 species was collected at PRKM 152.6. Mussel abundances (mussels/person-h and mussels/m2) ranged from 0.33 to 21.98 mussels/person-h and 0.00 to 2.24 mussels/m2. Recent recruitment (individuals < 40 mm, depending on the species) was observed for 15 species, including the endangered Epioblasma brevidens, Lemiox rimosus, and Quadrula intermedia. The greatest number of species (6) with evidence of recent recruitment also was found at PRKM 152.6. Data from the quantitative survey were used to simulate several sampling protocols that could be used to develop a long-term monitoring program for the Powell River. Five sites, PRKMs 197.9, 171.4, 159.6, 152.6, and 129.4, were selected for long-term monitoring because of high mussel densities and species richness. Six sampling protocols were simulated using the statistical program MONITOR to determine which protocols, if any, could monitor statistically significant changes in mussel abundance at rates + 10%. Each of the simulated sampling protocols lasted between 15 and 30 y, and employed quantitative sampling at 3 to 5 y intervals. None of the sampling protocols simulated during this study were able to detect declines in mussel abundance < 10%. Two sampling programs were able to detect increases in mussel abundance > 6% when the level of significance was > 0.10, and four sampling programs were able to detect a density increase of > 8% when the level of significance was 0.05. Despite the inability to monitor declines in mussel abundances, a long-term monitoring program is needed for the Powell River. Because qualitative sampling has been repeatedly shown to document species presence more effectively than quantitative sampling, it should be used to monitor changes in species presence and distribution. Quantitative sampling should be employed to monitor juvenile recruitment and changes in size-class structure of populations. Quantitative sampling also should be conducted to monitor overall mussel abundance at sites. Despite the inability to statistically detect changes in mussel density in the Powell River, quantitative sampling can provide valuable information, and the data collected can be used to qualitatively monitor changes in total density at sites. Both species share a similar distribution in the Powell River. Eighteen specimens of Quadrula sparsa were collected between PRKM 230.9 and 152.6, and 68 individuals of Q. intermedia were collected between PRKM 230.9 and 129.4. The highest density of each species was collected at PRKM 152.6, and recent recruitment was observed at PRKMs 152.6 and 153.4. Fresh-dead and relic shells of both species were thin-sectioned to determine individual growth rate and life span. These species complete the majority of their growth during the first 10 y of life, and likely live for a total of 40 to 50 y. One gravid female of Q. intermedia was collected during this study, but no gravid females of Q. sparsa were observed. / Master of Science