Using mouse teratocarcinoma system, we found a novel retinoic acid responsive gene. Midkine (MK), the product of the gene is a secreted, heparin-binding protein of molecular weight 14,000. MK gene is intensely expressed in the midgestation period, and in the adult mouse, the kidney is the principal site of its expression. MK and pleiotrophin have 50% sequence identity and constitute a new protein family regulating growth and differentiation. They share neurite outgrowth activity; other activities, either specific for one or common to both, have been reported. Furthermore, MK is of significant interest in cancer biology.