Mercury contamination of the North Fork Holston River below Saltville, Virginia has nearly extirpated most mussel populations. Because natural recovery of these populations has not occurred, this research combined field and laboratory assessments to determine the extent of ecological impairment in the river. In situ 60-day Asian clam (Corbicula fluminea) growth studies in 2005 showed a positive correlation (p=0.03) between low clam growth and sediment mercury levels. Because of severe low flow conditions of the NFHR in late 2005 conductivity dissipation from a point source brine discharge downstream rarely reached background level (~345 µS/cm) and was observed as high as 690 µS/cm 640 m below the discharge site. In addition, conductivity doubled in the river section adjacent to the remediated Ponds 5 and 6 (rm 81.6 and 80.4). Such low flow conditions (mean flow < 50 ft3/sec) occur in the NFHR approximately every five years. This low flow situation also evidenced a thick white flocculent or floc observed to accumulate at the base of the two remediated ponds. Analysis of the flocculent determined it to be high in aluminum (1.9-38 mg/L) and iron (2.0-51.0 mg/L), well above US Environmental Protection Agency Water Quality Criteria limits (0.0087 and 1.0 mg/L, respectively); riverine sediments collected below the accumulated floc also had high levels of calcium (240,000-380,000 mg/kg) and mercury(0.62-1.7 mg/kg). Acute tests with juveniles of Villosa iris and <24-hr old Ceriodaphnia dubia were used to measure the toxicity of the brine discharge, which had a conductivity of ~ 14,000 µS/cm. Results of these tests indicated C. dubia to be more sensitive than V. iris; however, chronic toxicity test results were similar for V. iris and C. dubia. The Lowest Observed Adverse Effect Concentration (LOAEC) for mussel survivorship after 28 days was 10,000 µS/cm, while the LOAEC for growth was 5,000 µS/cm. LOAECs for the C. dubia 7-day chronic were 25 % (survivorship) and 12.5 % (reproduction), while mean conductivity at these two concentrations was 4,054 and 2,211 µS/cm, respectively. Toxicity tests conducted with Pond 6 dyke cut discharges resulted in similar lethal concentrations for C. dubia and V. iris. Forty-eight hour LC50s of these discharges ranged from 12.07-15.95 % for C. dubia, and 17.36-18.95 % for V. iris. Dyke cut discharges also exhibited exceedingly high alkaline pH (11.5-12.2), which caused 100 % mortality to C. dubia in 15 min. The Pond 5 and 6 dyke discharges are the likely source for the flocculent accumulation at the base of the two remediated pond areas. The combined effect of mercury, aluminum and iron, along with periodic fluxes of high conductivity and alkaline pH during low flow conditions may contribute to low mussel recruitment downstream of Saltville, VA. / Master of Science