The effect of a cigarette-smoke condensate (CSC) and three CSC subfractions on the aldehyde dehydrogenase (ALDH; EC 1.2.1.3) activity in human blood cells was examined under physiological conditions in vitro. Incubation of intact or sonicated cells with different concentrations of crude CSC resulted in a dose-dependent reduction of the ALDH activity. The inactivation was only restored in part after extensive washing of the cells, indicating that the inhibition observed was mainly irreversible. The nonvolatile (NV) subfraction of the CSC caused a reduction in ALDH activity similar to that obtained with crude CSC, while the semivolatile (SV80) and volatile (SV20) subfractions did not significantly affect ALDH. The present results, showing that the human blood cell ALDH is inactivated by constituents of cigarette smoke in vitro, suggest that the blood ALDH activity reduction found in habitual smokers is also caused by components formed during the combustion of tobacco.