Sister chromatid exchanges (SCE) and lymphocyte subsets of children with acute lymphoblastic leukemia (ALL) were investigated during chemotherapy. The treatment followed protocol ALL-BFM-90. Children with ALL at the time of diagnosis showed statistically significant higher SCE frequencies (4.9 +/- 0.77) than healthy controls (3.6 +/- 0.93; P = 0.002). The in vivo effects of cyclophosphamide (CP) resulted in a dramatic increase of the SCE frequency (20.5 +/- 3.76). This increased SCE level of lymphocytes might reflect an instability of DNA or a deficiency of DNA repair. One could suggest that lymphocytes of children with ALL might have a higher susceptibility to harmful influences; and this could be a co-factor towards the development of the malignant disease. However, immediately 1 week after the administration of CP, the SCE rate decreased. This decline of SCE frequency correlated with a severe reduction of the absolute number of T lymphocytes. The observed reduction of SCE frequency may be due to a loss of T lymphocytes, or SCE became repaired during 1 week.