This Health Assessment Document for Diesel Engine Exhaust (DE) represents EPA's first comprehensive review of the potential health effects from ambient exposure to exhaust from diesel engines. The assessment was developed to provide information about the potential for DE to pose environmental health hazards, information that would be useful in evaluating regulatory needs under provisions of the Clean Air Act. The assessment identifies and characterizes the potential human health hazards of DE (i.e, hazard assessment) and seeks to estimate the relationship between exposure and disease response for the key health effects (i.e., dose-response assessment). The diesel engine has been a vital workhorse in the United States, powering many of its large trucks, buses, and farm, railroad, marine, and construction equipment. Expectations are that diesel engine use in these areas will increase due to the superior performance characteristics of the engine. Diesel engine exhaust (DE), however, contains harmful pollutants in a complex mixture of gases and particulates. Human exposure to this exhaust comes from both highway uses (on-road) as well as non-road uses of the diesel engine. EPA started evaluating and regulating the gaseous emissions from the heavy-duty highway use of diesel engines in the 1970s and particle emissions in the 1980s. The reduction of harmful exhaust emissions has taken a large step forward because of standards issued in 2000 which will bring about very large reductions in exhaust emissions for model year 2007 heavy-duty engines used in trucks, buses, and other on-road uses. A draft of this assessment, along with the peer review comments of the Clean Air Scientific Advisory Committee, was part of the scientific basis for EPA's regulation of heavy-duty highway engines completed in December 2000. The information provided by this assessment was useful in developing EPA's understanding of the public health implications of exposure to DE and the public health benefits of taking regulatory action to control exhaust emissions. EPA anticipates developing similarly stringent regulations for other diesel engine uses, including those used in non-road applications.