Using rat liver hepatocytes, we studied the effect of the tyrosine kinase inhibitor genistein on the Ca2+/IP3 (inositol 1,4,5-trisphosphate) and the cAMP (adenosine 3:5-cyclic monophosphate) transduction mechanisms. Genistein specifically blocked the activation of glycogen phosphorylase after EGF (epidermal growth factor). Genistein on its own partially activated phosphorylase and inactivated glycogen synthase. Genistein did not influence levels of IP3, but increased those of cAMP. This was especially clear when genistein was given together with glucagon. The data suggest an effect of a tyrosine kinase on the synthesis/degradation of cAMP.