Hypercalcemia is a common problem in renal transplant recipients, although in most cases, spontaneous resolution occurs within 1 year after renal transplantation. This condition may persist in some patients producing effects on renal function which are not well understood. In this study, we sought to analyze the effect of persistent hypercalcemia in the posttransplantation period on the function of renal transplants. A total of 121 recipients (31 women, 90 men; mean age, 34.1 +/- 9.9 years) underwent renal transplantation between 1999 and 2002. All patients underwent prospective evaluation of their serum calcium levels at 6-month intervals. A sustained corrected mean serum calcium level higher than 10.2 mg/dL was defined as "persistent hypercaicemia." Patients who had a gradual increase in their serum creatinine levels to > 2 mg/dL or a 50% rise above the baseline were considered to display chronic allograft dysfunction (CAD). Among 121 recipients, 52 patients (43%) developed CAD and 37 patients (30.6%) had persistent hypercalcemia. Among the CAD patients, 22 suffered persistent hypercalcemia, while the other 15 patients were without CAD, a difference that was statistically significant (42.3% vs 21.7%, P = .01). The mean calcium levels were lower among patients without than with CAD, a difference that did not reach statistical significance (9.9 +/- 0.4 mg/dL vs 1.0.1 +/- 0.6 mg/dL, P = .1). In conclusion, persistent hypercalcemia in the posttransplantation period may significantly contribute to the development of chronic allograft nephropathy.