Dioxins, furans, and trace metals were evaluated in shellfish and sediments from St. Louis Bay, Mississippi and adjacent waters of Mississippi Sound. Highest concentrations and the most toxic dioxin congener were found in St. Louis Bay sediments in closest proximity to the effluent outfall from the titanium dioxide refinery on the northern shore of the bay. Using conservative assumptions, we estimated the dioxin and furan burden of 17 measured congeners in St. Louis Bay sediments to be between 3.72 and 6.16 kg. Comparison of lipid-adjusted dioxins and furans in oysters (Crassostrea virginica) from this study with those collected from seafood markets and grocery stores in southern Mississippi in 1997 shows dioxin and furan contamination about 1.7 to 8 times higher in the samples from this study, depending on collection location. Oysters from St. Louis Bay and adjacent marine waters may accumulate higher concentrations of dioxins and furans than measured here, at other times during the year, due to the low lipid content of oysters in this single-season study. At other times, with typical higher oyster lipid levels, the dioxin content of oysters could increase by a factor of 8.5 to 12.7 times, commensurate with the expected increase in oyster lipids, although the rate of uptake of these contaminants is not known. Certain trace metals have increased markedly in St. Louis Bay shellfish since a 1978 baseline study that was conducted prior to the operation of the titanium dioxide refinery that produces large quantities of soluble waste metals such as chromium, nickel, and lead. In 2004, the percent value of chromium in oysters in St. Louis Bay was at least 1,167% greater than the 1978 values, and the percent value for nickel in oysters in the bay was at least 467% greater than the 1978 value. The percent value for chromium in 2004 from oysters outside the bay was between 7,700% and 11,300% greater than the 1978 reported in bay values. Rangia clams (Rangia cuneata) from St. Louis Bay tended to have greater increases than did oysters for all metals measured above detection limits in both studies, except for zinc, which declined in both shellfish species. Metals also increased in sediments, but soluble metals which are produced by, and apparently released from, the titanium dioxide refinery may be flushed out of the bay to higher salinity seawater before becoming adsorbed on fine silt and clay-size particles which are consumed by shellfish and/or deposited in sediments. Oysters from waters near the mouth of St. Louis Bay were also contaminated with dioxins, furans, and heavy metals. Based on widely published estimated safe and adequate daily dietary intake for chromium and nickel (the latter standard for hypersensitive individuals) the values recorded in this study indicate that less than one oyster per day should be consumed from the open harvest site sampled in adjacent Mississippi Sound. An evaluation of other regional sources of dioxin and dioxin-like compounds and heavy metals was conducted using data reported to the United States Environmental Protection Agency. Because of the lack of other identifiable large sources of these contaminants, the transport dynamics of soluble metals and the occurrence of highest dioxin and dioxin-like compound concentrations near the titanium dioxide refinery outfall, we conclude that the refinery is the most likely and most significant source of the measured dioxins, dioxin-like compounds, chromium, and nickel contamination found in St. Louis Bay and adjacent marine waters of Mississippi Sound.