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So-called epithelial rests of Malassez are derived from the Hertwig's root sheath and are located in the periodontal ligament, with still unknown functions. Different pathological conditions may lead to proliferation of these otherwise non-proliferative cell clusters. The insulin-like growth factor (IGF) system is an important growth factor system controlling proliferation and differentiation. In our study on Malassez cells from extracted human deciduous teeth, we investigated their structure by means of light and electron microscopy. Although they appeared as cellular clusters with a uniform epithelial phenotype, immunohistochemical analyses of components of the IGF system revealed an unique pattern: weak immunoreactivity could be seen for IGF-II while among all IGF binding proteins (IGFBPs) only IGFBP-6 and weakly IGFBP-4 were detectable in epithelial cells of Malassez. Since IGFBP-6 has a very high affinity for IGF-II and can inhibit its functions, we discuss that, in the normal periodontal ligament, autocrine IGFBP-6 may function as an antiproliferative molecule suppressing mitogenic effects of IGFs on Malassez cells.