Nephrotoxicity is the most important specific side effect of cyclosporine. After renal transplantation, differentiation between acute nephrotoxicity and graft rejection is an issue. This study correlates CsA levels with deterioration in renal function in nephrotoxicity episodes, and to evaluate the impact of dose reduction in minimizing the nephrotoxic effect of CsA. Method :Seventy - three renal transplant patients aged (16 - 65 y) who under went renal transplantation between (1989 - 1999), all on CsA (Neoral) therapy either in a dual or triple regimen have been included. 5. Blood and 24 hr urine sample were collected for each patient. Blood CsA level was measured by using HPLC. Renal function test, S.uric acid, 24 hr urine protein was performed too. Acording to clinical criteria, CsA level and graft function, the patients were classified in to three groups: - 1-Control group: Patients with normal graft function and CsA level ranged between 70 - 200 ng / ml. 2- Patients with CsA nephrotoxicity who showed an impairment in renal function. The mean CsA level measured for this group was 455 ng /ml. 3-Patients with allograft rejection who developed deterioration in renal function with a mean CsA level 109 ng / ml. Results: The mean CsA level in nephrotoxicity group was significantly different from that measured in control and rejection groups ( P < 0.005 ). CsA dose correlated positively and significantly with B.Urea and S.Creatinine in control group ( P < 0.005 and P < 0.01 ) respectively. There was a significant relationship between CsA level and each of B.Urea, S.Creatinine ( P < 0.05 ) and Creatinine clearance ( P < 0.005 ). While this relationship is not noticed in rejection group ( P > 0.05 ). No, significant correlation was observed between CsA level and each of S.Uric acid, S.K+, 24 hr urinary protein and urine volume / day in nephrotoxicity and rejection group while in control group a significant correlation was seen only between CsA level and each of 24 hr urine protein and urine volume / day. Renal function in patients with nephrotoxicity improved significantly P < 0.01 ) after reduction of Cs dose. Conclusion; - CsA level monitoring along with S.Creatinine is a good tool in differentoation between nephrotoxicity and rejection episodes and CsA nephrotoxicity is a dose and level dependent.