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Long-term contamination of the marine environment surrounding a lead smelter offered a unique opportunity to examine how pollutants might have acted to alter genetic characteristics of populations of organisms in the receiving system. This study used random amplified polymorphic DNA analysis to compare the genetic diversity of populations of the prawn, Leander intermedius, and the isopod, Platynympha longicaudata from the smelter discharge site with reference populations. The genetic diversity of the prawn population from the smelter discharge site (Port Pirie) was lower than that found in one reference population, and not significantly different from the other two reference populations. Genetic diversity of the Port Pirie population of isopods was found to be significantly lower than that of all reference populations. Prawns and isopods were also exposed to metal mixtures in the laboratory in a similar ratio to that found in seston near the smelter effluent discharge site. Both pre-exposed and reference populations of prawns tolerated elevated levels of metals and exhibited no significant difference in response. This contrasted with the isopods, with the pre-exposed isopod population showing greater tolerance to elevated metal levels compared with the reference population. These results highlight the need to include a number of reference populations for comparative purposes in genetic diversity studies, and the need to assess the influence of pollution on the genetic diversity of more than one species if genetic diversity analyses are to be used to gauge remediation success.