In polluted aquatic systems, sediments are the most important sink of contaminants and consequently as a source of pollutants to biota. Sediment bound contaminants may persist for many decades, for example, high concentrations of metals are still present in the Molonglo River sediments following the cessation of the Captains Flat mine operation in 1962. In this context, sediment is considered an important compartment to be investigated. The usefulness of H. depressa as a bioindicator to assess sediment toxicity was initially established by studying its exposure-dose-response to metal spiked sediment in laboratory microcosms. H. depressa was exposed to three different concentrations of single metal spiked sediment (cadmium, lead and zinc) for 28 days. Dose was measured by total accumulated metals in whole body and individual tissues and sub-cellular distribution of each metal was examined in hepatopancreas tissue. After 28 days exposure enzymatic and cellular biomarkers were measured as dose related responses. Despite high concentrations of metals in the sediments, exposure organisms accumulated relatively low concentrations of each metal. Labial palps accumulated significantly higher lead concentrations and gill accumulated significantly higher cadmium and zinc concentrations. A high percentage of all accumulated metals was detoxified and stored in metal rich granules. The biologically active metal fraction increased with metal exposure. Oxidative stress of H. depressa was evident from the biomarkers measured. Our response biomarker data indicated that metal exposure and dose significantly affected H. depressa indicating it would be a good bioindicator for evaluation of the health status of the Molonglo River.