Cyclosporin A (CyA) is a potent immunosuppressor used in organ transplantation and in the management of various autoimmune diseases. Gingival overgrowth is one of the side-effects of the CyA-treatment, affecting the attached gingiva of 25-81% of treated patients. To investigate the production and activity of matrix metalloproteinases (MMPs) in the CyA-induced gingival overgrowth, 2 well-documented models were utilized: the in vivo CyA-induced rat gingival overgrowth and primary cultures of human gingival fibroblasts treated with CyA. Our results obtained from the Western blot assays demonstrated clearly that the production of MMP-1 and MMP-3 was significantly inhibited by CyA at similar concentrations found in the serum of patients undergoing CyA-treatment. Moreover, the gelatinolytic activity of MMP-2 was also reduced both in cultured fibroblasts and in the rat CyA-induced gingival overgrowth. Taken together, the data presented here suggest that these inhibitory effects may contribute to the extracellular matrix (ECM) components accumulation in the CyA-induced gingival overgrowth.