This paper presents evidence that cigarette smoke condensate (CSC) is a potent inducer of sister chromatid exchanges (SCEs) in cultured human lymphocytes; that benzo(a)pyrene (BP) contributes very little to this activity; that smokers have higher SCE rates than nonsmokers; that smokers with untreated lung cancer have consistently higher basal and CSC-induced SCE rates than their matched heavy smoking controls; and that, on a weight-for-weight basis, CSCs from different tar categories of cigarettes induce similar numbers of SCEs. These results are in keeping with the evidence that many smokers die of lung cancer, and that the basis of malignant transformation may be an alteration in cellular DNA. The results raise questions about possible innate differences in individuals' responses to cigarette smoke, and about the "safeness" of lower tar cigarettes.