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Epidemiologic data suggest some associations between disinfection byproduct (DBP) exposure and human health risk. However, animal toxicology data show effects only at DBP doses considerably higher than environmental concentrations. This may be because human exposure to DBPs is typically at low levels. The major health risk posed by DBPs is likely to be caused by multiple, rather than single, exposures. Thus, DBP health effects and risk assessment cannot be fully characterized by single-chemical toxicology studies but are more appropriately addressed by research on DBP mixtures. This article outlines a structured approach to health-based research on DBP mixtures. Assessment guidance would stem from available data in three areas: the complex mixture of concern, a sufficiently similar mixture, and data based on components and interactions. Accurate evaluation of the human health risks associated with DBP mixtures can be achieved only through well-planned, structured experiments that are designed to address specific risk assessment issues, efficiently use resources, and are coordinated by a multidisciplinary team of scientists. Valid health-based information on DBP mixtures provided to water suppliers will improve assessments of drinking water quality and help utilities choose among treatment alternatives. Includes 43 references, figure.