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Mesocosms have been primarily used as research tools for the evaluation of the fate and effects of xenobiotic chemicals at the population, community, and ecosystem levels of biological organization. This paper provides suggestions for future applications of mesocosm research. Attention should be given to the configuration of mesocosm parameters to explicitly study regional questions of ecological interest. The initial physical, chemical, and biological conditions within mesocosms should be considered as factors shaping the final results of experiments. Certain fundamental questions such as the ecological inertia and resilience of systems with different initial ecological properties should be addressed. Researchers should develop closer working relationships with mathematical modelers in linking computer models to the outcomes of mesocosm studies. Mesocosm tests, linked with models, could enable managers and regulators to forecast the regional consequences of chemicals released into the environment.