Tyrosine kinase activity is associated with the transforming potential of several oncogenes. Human chronic myeloid leukemia (CML) cells and cell lines have been shown to contain an active bcr-c-abl p210 tyrosine kinase as a consequence of the Philadelphia chromosomal translocation. In the present work the activity of the c-abl and c-src oncogene-encoded tyrosine kinase was investigated during phorbol diester (TPA) induced differentiation of the K562 CML cells. The high tyrosine kinase activity of p210bcr-c-abl is strongly reduced during the initial 24 h of TPA treatment. In contrast, the activity of the c-src tyrosine kinase is not changed. No change occurs in the expression of the c-abl-specific RNAs during this period. Following the reduction of bcr-c-abl kinase activity, cell proliferation is arrested and megakaryoblastic antigens appear on the cells. Sodium butyrate caused a slight decrease in growth rate and of bcr-c-abl kinase activity during erythroid differentiation whereas no changes in c-src or c-abl tyrosine kinase activities were seen in DMSO-treated control cells.