Chromosome studies were performed on peripheral lymphocytes from two patients with Werner syndrome and two healthy control individuals to detect spontaneous and/or mutagen-induced chromosomal instability of this disease. Diepoxybutane, isonicotinic acid hydrazide, 4-nitroquinoline-1-oxide, and bleomycin were used as standard clastogens. While the spontaneous frequency of chromosomal breakage was much higher in lymphocytes from both patients than in the control cells, the basic rate of sister chromatid exchange (SCE) was found to be in the control range. The sensitivity to clastogens of the patients' cells, however, was not substantially increased as compared with the controls if the degree of multiplication of the spontaneous breakage rate or SCE frequency was taken as the basis for comparison. No indication of a greater inhibition of proliferation by the clastogens in the patients' cells than in normal cells was observed using BrdU-labelled lymphocytes. Thus, the lymphocytes from both patients of the present study lacked essential features of the classical chromosome instability syndromes.