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Blood or urine samples or both were obtained from 317 of 359 randomly selected tractor-trailer drivers asked to participate in a driver health survey conducted at a truck weighing station on Interstate 40 in Tennessee. Altogether, 29% of the drivers had evidence of alcohol, marijuana, cocaine, prescription or nonprescription stimulants, or some combination of these, in either blood or urine. Cannabinoids were found in 15% of the drivers' blood or urine; nonprescription stimulants such as phenylpropanolamine were found in 12%; prescription stimulants such as amphetamine were found in 5%; cocaine metabolites were found in 2%; and alcohol was found in less than 1%. These results provide the first objective information about the use of potentially abusive drugs by tractor-trailer drivers. The extent of driver impairment attributable to the observed drugs is uncertain because of the complex relationship between performance and drug concentrations.