The Philadelphia chromosome (Ph¹) is a translocation between chromosomes 9 and 22 that is found in chronic myelogenous leukemia (CML) and a subset of acute lymphocytic leukemia patients (ALL). In CML, this results in the expression of a chimeric 8.5-kilobase BCR-ABL transcript that encodes the P210^BCR-ABL tyrosine kinase. The Ph¹ chromosome in ALL expresses a distinct ABL-derived 7-kilobase messenger RNA that encodes the P185^ALL-ABL protein. Since the expression of different oncogene products may play a role in the distinctive presentation of Ph¹-positive ALL versus CML, it is necessary to understand the molecular basis for the expression of P185^ALL-ABL. Both P210^BCR-ABL and P185^ALL-ABL are recognized by an antiserum directed to BCR determinants in the amino-terminal region of both proteins. Antisera to BCR determinants proximal to the BCR-ABL junction in CML immunoprecipitated P210^BCR-ABL but not P185^ALL-ABL. Nucleotide sequence analysis of complementary DNA clones made from RNA from the Ph¹-positive ALL SUP-B15 cell line, and S1 nuclease protection analysis confirmed the presence of BCR-ABL chimeric transcripts in Ph¹-positive ALL cells. In Ph¹-positive ALL, ABL sequences were joined to BCR sequences approximately 1.5 kilobases 5′ of the CML junction. P185^ALL-ABL represents the product of a BCR-ABL fusion gene in Ph¹-positive ALL that is distinct from the BCR-ABL fusion gene of CML.