Blood specimens from 210 drivers (179 male and 31 female) apprehended in Luxembourg from autumn 2001 to spring 2002 and requested for the determination of their blood alcohol concentration (BAC) were tested for medicinal drugs, illicit drugs, and chronic alcohol abuse (by quantification of the carbohydrate-deficient transferrin: CDT). These additional analyses were performed anonymously and with permission of state prosecutor. The 22.8% had consumed medicinal drugs, with benzodiazepines and antidepressants (10.9 and 7.6%, respectively) as main psychoactive classes. Cannabis was the most detected illicit drug (9.5%) but only one in three had THC detectable in their blood. Association of two or more psychoactive substances (poly-drug use) was observed in 27.6% of drivers (90.6% of drug consumers). On the basis of CDT values, 29.5% of drivers investigated were assumed to be chronic alcohol abusers. Statistical analysis revealed that chronic alcohol abuse and medicinal psychoactive drugs were associated with significantly higher BAC. Medicinal psychoactive drugs were clearly associated with poly-drug use, and were furthermore detected at supra-therapeutic levels in 34.9%.