Immunohistochemical techniques were used to study the presence of cyclosporin A (CsA) and leukocyte subsets in 30 gingival biopsies of renal transplant subjects with gingival overgrowth (GO). Statistical analysis revealed significant differences in the total number of inflammatory cells determined by monoclonal antibody CD45, the monocyte/macrophage (CD68) subset, the plasmatic cells (EMA), and the total of T-lymphocytes (CD3) (P < 0.001, Student t test) between the treated subjects and the healthy control group. Differences were found in the helper/inducer T lymphocytes CD4 (P < 0.001 Student t test) and cytotoxic/suppressor T lymphocyte (CD8) (P < 0.01, Student t test) subsets between both groups. The CD4/CD8 ratio was greater in the transplant subjects than in the control group (1.82 +/- 0.16 versus 1.35 +/- 0.05 respectively) (P < 0.05 Student t test). There was no significant difference in the populations CD16+, CD57+, and CD20+. The CD45+ CD4+, and CD68+ cells increased in number along with the degree of GO. The number of epithelial cells/mm2 which displayed a deposit of CsA increased in accordance with the degree of GO (P < 0.05, Kruskal-Wallis's test). Likewise, the intraepithelial deposit of CsA in the GO region was found to be related to the inflammatory infiltrate CD4+, CD8+, and CD68+ (r = 0.7432; r = 0.7346; r = 0.77005, respectively). Our findings suggest that the intraepithelial deposit of CsA and the inflammatory infiltrate play a predominantly pathogenic role and are both related to the degree of GO.