Lead is a non-essential metal which is introduced into aquatic environments through anthropogenic activities such as mining. Lead accumulates in sediments can be toxic to aquatic biota. To assess the fate and effects of lead contaminated sediments on aquatic biota in freshwater ecosystems, the exposure-dose-response relationship of Hyridella depressa was investigated in laboratory microcosms. H. depressa was exposed to three different exposure concentrations of lead spiked sediments (7 ± 1, 205 ± 14 and 419 ± 16 µg/g) over 28 days. Dose was measured by lead accumulation in whole soft body and individual tissues. Sub-cellular distributions of lead and biological responses in terms of enzymatic and cellular biomarkers were measured in hepatopancreas tissues at day 28. Lead accumulation in whole body tissues were significantly increased over the exposure period and reflected sediment lead concentrations. Despite high concentrations of lead in the sediments, organisms accumulated relatively low lead concentrations (low treatment: 2.2 ± 0.2 µg/g, high treatment: 4.2 ± 0.1µg/g). Labial palps accumulated significantly more lead compared to other tissues. Of the lead accumulated in the hepatopancreas 83-91% was detoxified and stored in metal rich granules (MRG). The proportions and concentrations of lead in the MRG fraction increased with lead exposure. The biologically active lead was mainly present in the mitochondrial fraction and increased with lead exposure. Total antioxidant capacity significantly decreased while lipid peroxidation and lysosomal destabilation increased with lead exposure. The data indicated that H. depressa lead exposure resulted in lead doses that caused significant sub lethal health effects.