Tissue kallikrein is expressed in many species and is widely distributed throughout the body, including the brain. In general, this protease is well known to release the vasoactive peptide, kinin, from kininogen. We report here that kallikrein has a prominent growth-stimulating effect on neural stem cells prepared from the brains of prenatal rats. This growth-stimulating effect was suppressed by antiserum against rat tissue kallikrein. Since bradykinin B2-receptor antagonist, Hoe140, did not suppress the growth-stimulating effect, kallikrein-mediated kinin release does not appear to be involved in this effect. Thus, our data suggest a new physiological function of kallikrein, the growth of neural stem cells. Such involvement would suggest that kallikrein is not only potentially involved in an important function of brain development, but also available for studies on regenerative medicine for neurons.