The va &l protein is known to be a tyrosine-specific protein kinase. However, its normal cellular homolog, c-ah/P150, is not detectably phosphorylated on tyrosine in vivo or in vitro. The lack of associated tyrosine kinase activity for the c-ah/protein seems paradoxical since it is the c-ah/-derived sequences of the v-ah/protein that encode the kinase activity. We have detected an altered human c-ah/protein (P210) with associated tyrosine kinase activity in the K562 leukemia cell line. K562 cells are known to have a 9: 22 chromosomal translocation involving the c-abl locus and have amplified the c-abl gene 4 to 6 fold. The altered P210 human cab/is serologically and structurally related to the normal c-abl protein. A structural alteration of the human c-abl protein in K562 cells may have unmasked its associated tyrosine kinase activity. This altered c-abl protein may have important implications for a mechanism of activation of this oncogene.