Numerous studies have shown that dry weight concentrations of metals in sediments cannot be used to predict toxicity across sediments. However, several studies using sediments from both freshwater and saltwater have shown that interstitial water concentration or normalizations involving acid-volatile sulfide (AVS) can be used to predict toxicity in sediments contaminated with cadmium, copper, nickel, lead, or zinc across a wide range of sediment types. Six separate experiments were conducted in which two or three sediments of varying AVS concentration were spiked with a series of concentrations of cadmium, copper, lead, nickel, or zinc or a mixture of four of these metals. The amphipod Ampelisca abdita was then exposed to the sediments in 10-d toxicity tests. Amphipod mortality was sediment dependent when plotted against dry weight metals concentration but was not sediment dependent when plotted against simultaneously extracted metal (SEM)/AVS or interstitial water toxic units (IWTUs). Sediments with SEM/AVS ratios <1.0 were seldom (2.3%) toxic (i.e., caused <24% mortality), while sediments with SEM/AVS ratios >1.0 were frequently (80%) toxic. Similarly, sediments with <0.5 IWTU were seldom toxic (3.0%), while sediments with >0.5 IWTU were toxic 94.4% of the time. These results, coupled with results from related studies, demonstrate that an understanding of the fundamental chemical reactions which control the availability of cadmium, copper, lead, nickel, and zinc in sediments can be used to explain observed biological responses. We believe that using SEM/AVS ratios and IWTUs allows for more accurate predictions of acute mortality, with better causal linkage to metal concentration, than is possible with sediment evaluation tools which rely on dry weight metal concentrations.