Ezrin is a member of the TERM family and is a key protein in cytoplasmic membrane-cytoskeleton interactions. This study showed that hepatocyte growth factor/scatter factor (HGF/SF), a cytokine known to regulate motility, morphogenesis and growth of cells, stimulated the tyrosine phosphorylation of ezrin in a human colon epithelial cell line, HT115. After HGF/SF stimulation, ezrin translocated from the cytosol and generalised membrane to the areas of ruffled membrane as visualised by indirect immunofluorescent and immunogold electron microscopy. This effect was inhibited by genistein, a tyrosine kinase inhibitor. It is concluded that HGF/SF induces ezrin translocation by stimulation of its tyrosine phosphorylation and that this plays a key role in HGF/SF induced membrane ruffling.