Spontaneous and diepoxybutane (DEB)-induced sister chromatid exchanges (SCEs) were examined in cultured peripheral lymphocytes (PBL) from 122 healthy donors. SCE-inducing activity under defined experimental conditions and individual sensitivity to genotoxic stress were assessed. SCE means distribution appeared asymmetrical, identifying about 22% of subjects characterized by a 'high-respondent' phenotype with more than 111 SCEs/cell. Confounding factors, such as smoking habit, wine and coffee consumption, work activity and hematological factors, showed a limited capacity to affect individual SCE responsiveness, however hemoglobin and uric acid seemed to antagonize DEB genotoxicity.