This study has been designed to investigate the immunogenetic susceptibility of Cyclosporine-A (CsA) immunosuppressed renal transplant patients to development of gingival overgrowth, and the amplifying effect of calcium channel blockers on the severity of this clinical entity. 52 renal transplant recipients were selected and initially grouped as follows: group (Gp)1: CsA (n=7); Gp 2: CsA+verapamil (n=26); Gp 3: CsA+diltiazem (n=6); Gp 4: CsA+nifedipine (n=13). These groups were not found to be significantly different in age, sex, plaque index (PII), gingival index (GI), calculus index, periodontal probing depth, serum CsA level, or duration of CsA therapy (p>0.05). No significant (p>0.05) additive effect of the calcium channel blockers on the gingival overgrowth (GO) was assessed. The main group (n=52) was evaluated for the correlations between the clinical and the pharmacological variables and the GO. GI (rs=0.60) and the periodontal probing depth (rs=0.71) were found to be moderately correlated with the GO. The patients were regrouped based on the severity of overgrowth and recognized as responders (n=26) and nonresponders (n=26). Age, sex, calculus index, serum CsA level, duration of the CsA therapy, were not statistically different among these groups (p>0.05). P1I, GI, periodontal probing depth, and GO were significantly higher in the responder group (p>0.05). Analysis of HLA distribution of the responders and the nonresponders and comparison with the controls (n=3731) revealed that a statistically significant (p<0.001) % of the nonresponders were positive for HLA-DR1. These data would indicate that an immunogenetic predisposition should be suspected in the pathogenesis of the entity, and that HLA-DE 1 would have a protective role against gingival overgrowth induced by CsA.