This study evaluated the acute toxicity of four heavy metals (Pb, Zn, Mn, and Fe) to the freshwater gastropod Melanoides. For all metals, the LC50 increased as the mean exposure concentrations and periods decreased, respectively. The toxicity of these metals was arranged as follow Pb, then Zn, Fe, and Mn were, with Fe having the largest accumulation in the soft tissues. The survival rate of M. tuberculata (Stress on Stress) was decreased during the course of the exposure. The biochemical responses to heavy metal uptake in this snail showed that the Pb-treated group had the highest level of lipid peroxidation, but the actions of glutathione peroxidase (GPx), glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) revealed that the lowest activity of the enzyme was in the Pb-treated group, followed by the Zn-treated group, then Mn-treated group, while the Fe-treated group had the highest GPx, GST, CAT, and , SOD activity. The changes in the randomly amplified polymorphic DNA (RAPD) profiles could be induced by structural deformations produced by various kinds of DNA damage. The heavy metals accumulated in tissue of the gastropod M tuberculata caused oxidative stress and genetic changes.