A high concordance has been reported between fragile sites and breakpoints involved in chromosomal rearrangements in cancer. A prospective study on the role of fragile sites in the etiology of childhood acute lymphocytic leukemia (ALL), with appropriate comparisons to results obtained from normal controls, analyzed fluorodeoxyuridine-, aphidicolin-, and caffeine-induced fragile sites in the peripheral blood of seven ALL patients (three with cytogenetically normal karyotype and four with pseudodiploid karyotype) and eight normal controls. While extensive variations in the number and distribution of fragile sites was observed within each group, there was no significant difference in the mean total fragile sites and mean fragile sites per cell between the two groups (P greater than 0.05) in all three treatments. Similarly, within the ALL patients, the two karyotypic groups did not exhibit any significant difference in fragility (P greater than 0.05).