In the Eastern region of the Netherlands and the adjoining German region a survey on alcohol and cannabis consumption was conducted in order to trace differences and to explore to what extent these differences should be attributed to specific national determinants. The reason for initiating the study was the differences between both countries with regard to drug policies, which proved to be an obstacle for bordercrossing cooperation. A stepwise regression analysis at the individual level was applied in the German and Dutch samples separately, to determine the sets of variables associated with the substance use for each country. It is concluded that variances in substance use within and between both countries are mainly attributed to lifestyle characteristics which vary considerably within both countries. The higher prevalence of drunkenness in Germany and of cannabis use among Dutch adolescents, largely has to be attributed to an unequal distribution of these determinants in the countries. The possible impact of national regulations on the patterns of substance use is discussed.