High treatment costs force the discontinuation of cyclosporine (CSA) in a vast majority of renal transplant recipients in India. The impact of CSA withdrawal among 108 living related renal transplant recipients 12.54 +/- 4.2 months after transplantation was studied retrospectively. In 83 patients, CSA was withdrawn over a 12-week period (group I). Azathioprine dosage was increased to 2 to 2.5 mg/kg/d, and prednisolone, to 30 mg/d 2 weeks and 1 week before starting CSA withdrawal, respectively. In the other 25 patients, CSA had to be withdrawn faster (mean, 28.52 +/- 14.18 days; group II). Twenty-nine rejection episodes (26.9%) were noted in 22 patients (20.4%; 19% in group I and 52% in group II; P: = 0.008). Fifteen group-I patients (18%) and 11 group-II patients (44%) died or lost their grafts (P: = 0.017). There was no difference in age, donor source, HLA matches, pretransplantation cross-match positivity, delayed graft function, immunosuppressive drug doses, rejection episodes, or prewithdrawal serum creatinine levels between the patients who did or did not develop acute rejection after CSA withdrawal. On follow-up, 10 patients (50%) died or returned to dialysis among the rejection group compared with 16 patients (18%) in the nonrejection group (P: = 0.007). The mean creatinine level at last follow-up was greater in the rejection group (3.97 +/- 2.54 versus 1.65 +/- 1.1 mg/dL; P: < 0.001). CSA withdrawal because of economic constraints carries a significant risk for acute rejection and death and/or graft loss in Indian living donor renal transplant recipients, even after 12 months.