The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from the reciprocal translocation t(9;22) (q34;q11). On DNA level a BCR/ABL rearrangement involving the so-called major BCR (Mbcr) from chromosome 22 has been associated with chronic myeloid leukemia (CML). For Ph+ ALL a site of rearrangements in the 5' part of the BCR (breakpoint cluster region) gene on chromosome 22, the so-called minor bcr region (mbcr) has been described within the first intron in a 10.8 kb region (=bcr2 or m-BCR1). The BB1 probe detects two Eco fragments of 8.5 and/or 11 kb, which may appear as monomorphic or heteromorphic alleles, both covering bcr2. We have analyzed EcoRI restriction polymorphisms within bcr2 in 42 patients with a rearrangement in M-bcr (including 39 Philadelphia chromosome-positive (Ph+) CML patients and 3 ALLs) and in 18 healthy unrelated volunteers. Of the 42 patients tested, 52.4% (22) had the 8.5 kb bcr2 allele, 21.4% (9) had the 11 kb bcr2 allele, and 26.2% (11) had both the 8.5 and the 11 kb allele. In addition to normal allelic polymorphisms in bcr2, rRFs (rearranged bcr2 restriction fragments) were found in bcr2 as shown in 33% (14 of 42) of our patients. By contrast, no rRFs were found in 18 healthy volunteers. Our results indicate, that heterogeneous rearrangements in bcr2 may appear in addition to BCR/ABL rearrangements involving M-bcr in Ph+CML.