The aldehyde dehydrogenase (ALDH; EC 1.2.1.3) activity was determined in samples of whole blood and in isolated erythrocytes and leukocytes from users of Swedish moist snuff, cigarette smokers and non-tobacco-using controls. The mean whole blood ALDH activity of the smokers was reduced by 21% (p less than 0.001) when compared to the controls, while that of the snuff users was reduced by only 8% (not significant). Similar but somewhat less pronounced differences were obtained both in the assays with erythrocytes and leukocytes. In the cigarette smokers, the whole blood activity correlated significantly (r = -0.79, p less than 0.001) with the plasma concentration of cotinine, the major metabolite of nicotine, whereas no correlation was observed for the users of moist snuff. Similar plasma nicotine and cotinine levels were found in smokers and snuff users, which indicates that the reduced blood ALDH activity in smokers is not caused by nicotine or any of its metabolites, but more likely, by components formed during combustion of tobacco. Since a reduced blood ALDH activity has previously been suggested as an indicator of excessive alcohol consumption, the present results show that, in future studies on blood ALDH, the smoking habits should also be taken into account.