In this report the authors describe the characterization of a cytosolic tyrosine kinase activity (IL-6PTK) stimulated by interleukin 6 (IL-6). IL-6PTK appears 6 h after IL-6 addition and is inhibited by tyrphostin but not genistein. It is active under its phosphorylated form although it is not immunoprecipitated by antiphosphotyrosine antibodies, suggesting that autophosphorylation occurs on residues other than tyrosine. Using the ATP-binding site covalent label, 5'-p-fluorosulfonylbenzoyladenosine (FSBA), two phosphoproteins have been identified of 52 and 59 kDa respectively, that could potentially harbour IL-6PTK activity. The intracellular elevation of cAMP, which inhibits 7TD1 cell proliferation, decreases as the same time IL-6PTK activity suggesting that the cAMP-dependent kinase could act as a negative regulator of this tyrosine kinase species. Taken together the results strongly suggest that a tyrosine kinase (IL-6PTK) might be involved in the cascade of events leading to the proliferation of 7TD1 cells under IL-6 stimulation.