Chronic myelogenous leukemia (CML) is a clonal hematologic malignancy characterized by a reciprocal translocation between chromosomes 9 and 22 [t(9;22)] in greater than 90% of cases. This translocation results in a short chromosome 22, termed the Philadelphia (Ph1 or 22q-) chromosome. Recently, the cellular oncogenes abl and sis were mapped to human chromosomes 9 and 22, respectively. Moreover, abl was shown to be translocated from chromosome 9 to 22 and sis from chromosome 22 to 9 in CML patients with t(9;22). These findings raised the possibility that one or both of these oncogenes is activated and directly involved in the development of the disease. We analyzed expression of the abl and sis oncogenes in leukemic cells from CML patients with t(9;22). We found that sis is not expressed but that abl is transcribed into an 8-kilobase RNA. This abl RNA is also present in two leukemic cell lines (EM2 and K562), which were derived from CML patients and contain the t(9;22). This 8-kilobase RNA is not detected in normal cells, in other human leukemias without t(9;22), or in human cell lines that lack t(9;22). The consistent presence of this abl RNA transcript in CML with t(9;22) suggests that it is a consequence of abl translocation and that it plays a role in the development of this leukemia.