To further understand the biological function of translationally controlled tumor protein (TCTP), also known as IgE-dependent histamine-releasing factor (HRF), the yeast two-hybrid system was used to screen interacting molecules. We isolated cDNA clones coding for TCTP/HRF, suggesting that it may have a self-interacting property. Domain mapping of the interaction revealed that the C-terminal region of residue 126–172 is involved in self-interaction. The self-interacting property of TCTP/HRF was further supported by FPLC gel-filtration chromatography and coimmunoprecipitation analysis from transfected COS-7 cells. Our data suggests that TCTP/HRF may have a potential to self-interact through the C-terminal region, and the self-interaction property may be related to its biological function.