Hepatocyte growth factor (HGF) stimulates inositol 1,4,5-trisphosphate (InsP3) formation in rat primary cultured hepatocytes, which is inhibited by the pretreatment with a tyrosine kinase inhibitor, genistein. This InsP3 production was coincident with tyrosine phosphorylation of phospholipase C gamma (PLC gamma), detected in immunoprecipitates with anti-PLC gamma, suggesting activation mechanism of PLC gamma by tyrosine phosphorylation. However, in human hepatocarcinoma HepG2 cells, HGF, which suppresses cell growth, causes neither phosphorylation of PLC gamma nor InsP3 formation. The results suggests that PLC gamma in normal hepatocytes was activated by HGF through tyrosine kinase of HGF receptor.