The ultimate goal of clinical periodontal therapy is to achieve regeneration of a healthy connective tissue reattachment. Conventional therapy including scaling, root planing, gingival curettage, gingivectomy and flap procedures of various types results primarily in repair rather than regeneration of the periodontium. In order for periodontal regeneration to occur, progenitor periodontal ligament cells must migrate to the denuded root surface, attach to it, proliferate and mature into an organized and functional fibrous attachment apparatus. Polypeptide growth factors belong to a class of potent biologic mediators which regulate cell differentiation, proliferation, migration and metabolism. Insulin like growth factor I (IGF- I ) of these factors appear to have an important role in periodontal wound healing and bone formation. The purpose of this study is to evaluate the effects of IGF- I on the periodontal ligament cells to use as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were obtained from periodontal tissue explants culture of the first premolar tooth extracted for the orthodontic treatment. Cells were cultured in Dulbeccos modified Eagle medium(DMEM) with 10% fetal bovine serum. Fourth to seventh passage cells were plated in 24 well tissue culture plates and medium changed to serum free medium prior to addition of growth factors. Cell proliferation was measured by the incorporation of [H] thymidine into DNA, Protein synthesis was determined by measurement of [H] proline incorporation into collagenase digestible protein(CDP) and noncollagenous protein(NCP) according to the method of Peterkofsky and Diegelmann (1971), And alkaline phosphatase activity was measured as one parameter of osteoblastic differentiation. The results were as follows ' The DNA synthetic activity was increased in a dose dependent manner with IGF- I except for 0.1ng/ml concentration of IGF- I At the concentration fo 10, 100ng/ml, IGF- I significantly increased the DNA synthetic activity(P<0.05) The total protein, collagen and noncollagen synthesis was increased in a dose dependent manner with IGF I except for 0.1ng/ml concentration of IGF-I. At the concentration of 1, 10, 100ng/ml, IGF-I significantly increased the total protein, collagen and noncollagen synthesis activity(P<0.95, P<0.001). The % of collagen was not effected according to the concentration of IGF- I . The alkaline phosphatase activity was increased in a dose , time dependent manner with IGF- I (10, 100ng/ml). In conclusions, the present study shows that IGF I has a potentiality to enhance the DNA synthesis of periodontal ligament cells with including the increase of the total protein and collagen synthetic activity. The use of IGF- I to mediate biological stimulation of periodontal ligament cells shows promise for future therapeutic applications.