Cyclosporine A, an extremely effective immunosuppressant, is also associated with various untoward effects, including gingival overgrowth. Despite intense clinical and laboratory investigation, the cellular-molecular mechanism through which cyclosporine A simultaneously acts as a selective immunosuppressant while it elicits a connective tissue reaction in the gingiva remains poorly understood. In recent years, cellular and molecular biologic techniques have elucidated a variety of growth factors that control connective tissue homeostasis. Two growth factors known to be major elements in wound repair and connective tissue homeostasis are platelet-derived growth factor and transforming growth factor-b1. Increased gingival levels of these factors may be responsible for promoting fibroblastic proliferation and fibroblastic production of extracellular matrix constituents in overgrown gingival tissues. Expression of these factors has recently been shown to be upregulated in these tissues. The results of these recent studies may provide a foundation for understanding the molecular mechanism involved in the pathogenesis of cyclosporine A-induced gingival overgrowth.