Cigarette smoking has been shown to affect human immune responses. We have studied Fas/Fas ligand (FasL) expression, which is involved in the cytotoxic activity, immune privilege, and self-tolerance, and other apoptosis-associated molecule expression of peripheral blood lymphocytes (PBL) in healthy subjects with/without cigarette smoking. We found that expression of Fast protein was detected marginally in the fresh PBL and was induced upon mitogen activation in normal individuals without smoking. In contrast, fresh PBL from those with chronic cigarette smoking exhibited enhanced expression of Fast protein without in vitro mitogen stimulation. Moreover, mitogen stimulation failed to augment Fast protein expression of their lymphocytes, suggesting dysregulation of Fast expression of PBL in individuals with cigarette smoking. In contrast, Fas, Bcl-2, and p53 expression were not significantly different between normal individuals with chronic cigarette smoking and those without smoking. In addition, we found that in vitro brief treatment with nicotine induces and/or enhances Fast mRNA and protein expression of lymphocytes from normal donors without smoking. These results suggest that aberrant Fast expression of lymphocytes is, at least in part, involved in the immune impairment in individuals with chronic cigarette smoking, (C) 1999 Academic Press.