Medical management is still far from optimal in secondary hyperparathyroidism. This may be explained, at least in part, by genetic differences. The aim of this study was to evaluate the association of genetic influences of angiotensinconverting enzyme (ACE) gene polymorphisms with response to vitamin D therapy among patients on hemodialysis (HD). Eighty-two patients (female/male, 34/48; mean age, 47.5+/-15.3 y; HD duration time, 76.6+/-33.2 mo) with endstage renal disease who were on maintenance HD were included in the study. Five-year retrospective demographic, clinical, laboratory, and treatment data (5-y cumulative doses of phosphate-binding drugs and oral and intravenous cumulative doses of active vitamin D) were retrieved from patients' hospital records. ACE gene polymorphisms of patients were documented and were used to group patients as follows: The insertion/deletion polymorphism group (I/D) consisted of (1) group non-DD (n=43), who had the DI or II allele, and (2) group DD (n=39), who had the DD allele. Patients with the DD allele (group DD) of ACE gene polymorphism had (1) significantly elevated mean 5-y intact parathyroid hormone levels when compared with the non-DD group (P=.009), and (2) significantly elevated oral and intravenous 5-y cumulative doses of vitamin D. Oral and intravenous 5-y cumulative doses of vitamin D used in group DD patients were significantly higher than those in group I patients (P=.038 and P=.037, respectively). Knowledge of genetic differences among patients on HD may be useful to the clinician in planning treatment strategy. ACE gene polymorphism may have an effect on hyperparathyroidism, as is seen in patients on HD. Patients from this group who have resistant hyperparathyroidism may be candidates for ACE inhibitor therapy.