The aim of this study was to evaluate, clinically and histologically, the effect of Cyclosporin-A (CyA) on the progression of the periodontal breakdown in the domestic ferret, using the ligature induced periodontitis model. At the start of the experiment (day 0), silk ligatures were placed at the gingival margin level of experimental teeth. The contralateral teeth served as non-ligated control teeth. Clinical measurements included gingival index, probing pocket depth (PPD), probing attachment level (PAL) and gingival overgrowth (GO) and they were performed on days 0, 14 and 28. Cyclosporin-A, 10 mg/kg/d, was given subcutaneously from day 0 to 21, while in the last week there was a reduction of this dose to 5 mg/kg/d. Blood samples were taken on days 0, 14 and 28. On day 28 the animals were sacrificed. Histological sections were prepared for ligth microscopy. The histometric measurements performed were: (1) the distance between cementoenamel junction and the alveolar bone crest and (2) loss of connective tissue attachment. The number of sections with root resorption areas was observed. Cell counts were taken in 4 different areas. The results showed, on days 14 and 28, a significant increase of the mean values of PPD and PAL at experimental teeth as compared to the control teeth. GO was present on experimental teeth on days 14 and 28. On day 28, the control teeth presented a very small increase in GO, mainly at the buccal sites of P4 and M1. The histometric results showed a significant loss of attachment and bone resorption in the experimental teeth. Root resorption was found in experimental teeth only. The predominant inflammatory cell in the 4 experimental areas was polymorphonuclears. The number of plasma cells and lymphocytes was also significantly higher in experimental teeth than in control teeth. The results indicate that the T-cell immunosystem may participate in defensive mechanisms against periodontal pathology in the domestic ferret, GO may be induced in ferrets under treatment with CyA and this result may be obtained quickly in sites where ligatures have been placed.