In chronic myelogenous leukemias (CML) with the t(9;22)(q34;q11) chromosome translocation the breakpoints on chromosome 22 occur within a 5.8-kilobase segment of DNA referred to as "breakpoint cluster region" (bcr). The same cytogenetically indistinguishable translocation occurs in approximately 10% of patients with acute lymphocytic leukemias (ALL). In this study we have investigated the chromosome breakpoints in several cases of ALL carrying the t(9;22) translocation. In three of five cases of ALL we found that the bcr region was not involved in the chromosome rearrangement and that the 22q11 chromosome breakpoints were proximal (5') to the bcr region at band 22q11. In addition, we observed normal size bcr and c-abl transcripts in an ALL cell line carrying the t(9;22) translocation. We conclude, therefore, that if c-abl is inappropriately expressed in ALL cells without bcr rearrangements, the genetic mechanism of activation must be different from that reported for CML.