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Emissions from heavy-duty vehicles in real operation on the road often differ greatly from those that would be projected from laboratory testing. Reasons for this difference include variations between laboratory and real-world driving conditions, wear and deterioration that are not effectively modeled by laboratory tests, inadequate or inappropriate in-use maintenance, and the use of “cycle-beating” strategies and “defeat devices” by engine manufacturers. This paper analyzes data showing in-use emissions from heavy-duty diesel and natural gas vehicles tested using various driving cycles on chassis dynamometers. It is shown that average in-use emissions of particulate matter (PM) and oxides of nitrogen (NOx) from late model heavy-duty diesel engines are much higher than predicted by current emission models, and greatly exceed the emission standards to which these engines were certified.