The Anniston Polychlorinated Biphenyl (PCB) Site is located in the vicinity of the municipality of Anniston in Calhoun County, in the north-eastern portion of Alabama. Although there are a variety of land-use activities within the Choccolocco Creek watershed, environmental concerns in the area have focused mainly on releases of PCBs to aquatic and riparian habitats. PCBs were manufactured by Monsanto, Inc. at the Anniston facility from 1935 to 1971. The chemicals of potential concern (COPCs) in sediments at the Anniston PCB Site include: PCBs, mercury, metals, polycyclic aromatic hydrocarbons (PAHs), organochlorine and organophosphorous pesticides, volatile organic compounds (VOCs), semivolatile organic compounds (SVOCs), and polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs). The purpose of this study was to evaluate the toxicity of PCB-contaminated sediments to the juvenile fatmucket mussel (Lampsilis siliquoidea) and to characterize relationships between sediment chemistry and the toxicity of sediment samples collected from the Anniston PCB Site using laboratory sediment testing. Samples were collected in August 2010 from OU-4 of the Anniston PCB Site, as well as from selected reference locations. A total of 32 samples were initially collected from six test sites and one reference site within the watershed. A total of 23 of these 32 samples were evaluated in 28-day whole-sediment toxicity tests conducted with juvenile mussels (L. siliquoidea). Physical and chemical characterization of whole sediment included grain size, total organic carbon (TOC), nutrients, PCBs, parent and alkylated PAHs, organochlorine pesticides, PCDD/PCDFs, total metals, simultaneously extracted metals (SEM), and acid volatile sulfide (AVS). Sediment collected from Snow Creek and Choccolocco Creek contained a variety of COPCs. Organic contaminants detected in sediment included PCBs, organochlorine pesticides, PCDDs/PCDFs, and PAHs. In general, the highest concentrations of PCBs were associated with the highest concentrations of PAHs, PCDDs/PCDFs, and organochlorine pesticides. Specifically, sediments 08, 18, and 19 exceeded probable effect concentration quotients (PEC-Qs) of 1.0 for all organic classes of contaminants. These three sediment samples also had high concentrations of mercury and lead, which were the only metals found at elevated concentrations (i.e., above the probable effect concentration [PEC]) in the samples collected. Many sediment samples were highly contaminated with mercury, based on comparisons to samples collected from reference locations. The whole-sediment laboratory toxicity tests conducted with L. siliquoidea met the test acceptability criteria (e.g., control survival was greater than or equal to 80%). Survival of mussels was high in most samples, with 4 of 23 samples (17%) classified as toxic based on the survival endpoint. Biomass and weight were more sensitive endpoints for the L. siliquoidea toxicity tests, with both endpoints classifying 52% of the samples as toxic. Samples 19 and 30 were most toxic to L. siliquoidea, as they were classified as toxic according to all four endpoints (survival, biomass, weight, and length). Mussels were less sensitive in toxicity tests conducted with sediments from the Anniston PCB Site than Hyalella azteca and Chironomus dilutus. Biomass of L. siliquoidea was less sensitive compared to biomass of H. azteca or biomass of larval C. dilutus. Based on the most sensitive endpoint for each species, 52% of the samples were toxic to L. siliquoidea, whereas 67% of sediments were toxic to H. azteca (based on reproduction) and 65% were toxic to C. dilutus (based on adult biomass). The low-risk toxicity threshold (TTLR) was higher for L. siliquoidea biomass (e.g., 20,400 µg/kg dry weight [DW]) compared to that for H. azteca reproduction (e.g., 499 µg/kg DW) or C. dilutus adult biomass (e.g., 1,140 µg/kg DW; MacDonald et al. 2014). While mussels such as L. sili