The role of the tyrosine kinase signal transduction pathway was investigated in human colon solid tumors and colon tumor cell lines. A high level of tyrosine kinase activity was found in 7 of the 27 human solid tumors tested (26%). In these cases, a close correlation between the level of tyrosine kinase activity and the high ratio of the S phase cells has been demonstrated (r = 0.8418). High autophosphorylation accompanied by a high proliferation capacity was detected in 8 cases (29.6%). In 12 cases (44%) low tyrosine kinase activity with a lower proliferation rate was found. Seven of the 8 human colon tumor cell lines tested showed tyrosine kinase activity. Differentiation-inducing agents, such as sodium butyrate and retinoic acid, have been applied to influence the rate of cell proliferation. Treatment with 5 mM sodium butyrate (24 h) and 10 microM retinoic acid (48 h) effectively decreased the fraction of S phase cells and 3H-thymidine incorporation. The tyrosine kinase activity fell to 9-22% and to 44-65% of the original value in the case of the sodium butyrate and retinoic acid treatment, respectively. Our results suggest that a significant part of human colon tumors have an active tyrosine kinase signal transduction pathway and that tyrosine kinase plays a role in the process of proliferation rather than in the process of differentiation in these human colon tumor cell lines.