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Introduction. Several factors can influence the gingival tissues such as disrupting tissue homeostasis and the occurrence of pathological conditions. The aim of our study was to investigate and compare the presence of apoptosis in patients undergoing immunosuppressive therapy, patients with periodontitis and healthy patients, as well as to achieve better understanding of the role of apotosis in the same processes. Methods. The first examined group consisted of 21 patients (10 males and 11 females; mean age 37.4± 10.2 years) with neither kidney diseases nor cyclosporine A (CsA) therapy, who had a verified periodontal disease. The second group consisted of 21 kidney-transplant patients (9 males and 12 females), with diagnosed gingival overgrowth (GO) undergoing continuous immunosuppressive therapy. The control group consisted of the same number of patients, clinically healthy subjects (15 males and 6 females; mean age 29 ± 4.0 years) with plaque-induced gingivitis. The following indexes were analyzed: plaque index (PI), index of gingival inflammation (GI) according to Loe-Silnes, and gingival overgrowth index (GOI) according to MacGaw, et al. The determination of CsA in blood was performed by a fluorescence polarised immunoassay (FPIA). The tissue samples were estimated by semi-quantitative analysis in order to determine the presence of apoptotic cells and imunohistochemical expression of the bcl-2 and p53 proteins. Results. In our study we found statistical differences in bcl-2 and apoptotic index, among the groups: the greatest expression of bcl-2 and apoptotic index was registered in the group treated with CsA, and the lowest expression was noted in the gingivitis group (p<0.01). There was a statistical significant positive correlation between bcl-2 and apoptotic index, PI, and GI index (p<0.05). There was no significant correlation between the blood concentration of CsA and apoptosis (p>0.05; r=0.187). Conclusions. Our findings suggest that increased apoptosis may have a role in the pathogenesis of CsA-induced gingival overgrowth in the cases of patients on high dose of CsA. [ABSTRACT FROM AUTHOR]