We have carried out a screening for loss of heterozygosity (LOH) in 51 children with B-lineage acute lymphoblastic leukemia (ALL). Forty-six highly polymorphic microsatellite markers located in subtelomeric areas of every chromosome arm were analyzed in each patient. Allelic losses were encountered at 21 of the 46 loci tested (46%). The frequency of LOH at a given locus was usually < 10% and fractional allelic loss, calculated as the ratio of chromosomal arms displaying loss among all informative arms for each patient, ranged from 0.025 to 0.31 (mean, 0.063). This study provides further evidence that deletional events are a major type of genetic alteration found in childhood ALL. The diversity of the loci displaying LOH suggests that, as in solid tumors, numerous tumor suppressor genes are likely to participate in leukemogenesis. However, the overall low frequency of LOH, as well as the absence of microsatellite instability suggest that the genetic instability is lower in childhood ALL than in most of the solid tumors.