Activation of the abl gene and its involvement in human leukemia is one of the most thoroughly characterized examples of the structural alterations of chromosomes associated with the conversion of a normal cell into a cancer cell. The abl oncogene as first identified on the Abelson murine leukemia virus (A-MuLV). Activation of the viral oncogene is associated, in part, with the truncation of the gene at its 5' end. As in studies with other retroviruses, results with A-MuLV presaged the mechanism of activation by abl in naturally occurring human malignancies. Thus, chronic myelogenous leukemia (CML) is consistently associated with a translocation of a piece of chromosome 9 onto chromosome 22 creating what is known as the Philadelphia chromosome (Ph1). The result of this translocation is the truncation of the 5' end of the cellular abl gene, which is located at the breakpoint of chromosome 9. The function of the abl gene product is poorly understood but is thought to participate in an, as yet, undefined pathway of growth control signals, which originate outside the cell, and traverse through the cell into its nucleus. The loss of the gene product's N-terminal amino acid sequences brought about by the truncation of the 5' portion of the gene is consistent with the hypothesis that the protein's growth-controlling activity is deregulated by the structural alterations which occur in the cancer cells. The abl gene and CML serve as a paradigm of the mechanism of activation of proto-oncogenes by chromosomal alterations. The case of CML and the Ph1 chromosome illustrates the findings we might expect as other chromosomal abnormalities are characterized at the molecular level.