Little is known regarding mixture effects of metals and polynuclear aromatic hydrocarbon (PAHs) under environmentally relevant exposure regimes. Standard U.S. Environmental Protection Agency (U.S. EPA) procedures were applied and extended to test effects of phenanthrene (Phen) on sediment-Cd uptake, aqueous-Cd uptake, and Cd-elimination kinetics in the amphipod Hyalella azteca. In sediment exposures, Phen increased the projected equilibrium-tissue concentration of Cd from 47.2 (36.2–58.3) to 221.1 μg/g ([117.8–324.3], 95% confidence intervals [CI] in parentheses). Although Cd bioaccumulation increased markedly in sediment exposures, dissolved Cd concentrations and physical-chemical parameters indicative of Cd bioavailability were unaffected by Phen. Further, in water-only exposures, Phen had no effect on Cd bioaccumulation or Cd-elimination kinetics. These results indicate that increased Cd bioaccumulation in Cd-Phen mixtures occurred via a sediment-mediated process and was likely a function of increased uptake associated with feeding (i.e., Pheninduced alterations in ingestion and/or digestive processes). Observed increases in H. azteca lethality when exposed to Cd-Phen mixtures in sediment, but not in water-only exposures, likely resulted from increased Cd bioaccumulation rate rather than a true toxicological synergism. Thus, apparent synergisms and antagonisms may result from exposure-mediated effects in sediment that are unrelated to toxicological interactions. Implications of these findings regarding sediment-quality assessment and suggestions for future studies are discussed.