Chemical disinfection of water is a major public health triumph of the 20th century. Dramatic decreases in both morbidity and mortality of waterborne diseases are a direct result of water disinfection. With these important public health benefits comes low-level, chronic exposure to a very large number of disinfection byproducts (DBPs), chemicals formed through reaction of the chemical disinfectant with naturally occurring inorganic and organic material in the source water. This article provides an overview of joint research planning by scientists residing within the various organizations of the U.S. Environmental Protection Agency Office of Research and Development. The purpose is to address concerns related to potential health effects from exposure to DBPs that cannot be addressed directly from toxicological studies of individual DBPs or simple DBP mixtures. Two factors motivate the need for such an investigation of complex mixtures of DBPs: a) a significant amount of the material that makes up the total organic halide and total organic carbon portions of the DBPs has not been identified; and b) epidemiologic data, although not conclusive, are suggestive of potential developmental, reproductive, or carcinogenic health effects in humans exposed to DBPs. The plan is being developed and the experiments necessary to determine the feasibility of its implementation are being conducted by scientists from the National Health and Environmental Effects Research Laboratory, the National Risk Management Research Laboratory, the National Exposure Research Laboratory, and the National Center for Environmental Assessment.