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Abstract: Dextromethorphan is a nonprescription antitussive which has been gaining in popularity as an abused drug, because of the hallucinogenic, dissociative, and intoxicating effects it produces at high doses. This report describes a series of eight drivers arrested for driving under the influence of the combined effects of dextromethorphan and chlorpheniramine, and a further four drivers under the influence of dextromethorphan alone. In the combined dextromethorphan/chlorpheniramine cases, blood dextromethorphan concentrations ranged from 150 to 1220 ng/mL (n = 8; mean 676 ng/mL, median 670 ng/mL), and chlorpheniramine concentrations ranged from 70 to 270 ng/mL (n = 8; mean 200 ng/mL, median 180 ng/mL). The four cases without chlorpheniramine present had blood dextromethorphan concentrations between 190 and 1000 ng/mL (mean 570 ng/mL, median 545 ng/mL). Some drivers had therapeutic concentrations of other drugs present. Drivers generally displayed symptoms of central nervous system (CNS) depressant intoxication, and there was gross evidence of impairment in their driving, including weaving, leaving the lane of travel, failing to obey traffic signals, and involvement in collisions. Drug Recognition Expert opinions confirmed that the subjects were under the influence of a drug in the CNS-depressant category.