The search for more effective and less toxic immunosuppressive agents is conducted around the globe. In this study effect of reduction and omission of cellcept and azathioprine (AZA) in standard immunosuppressive regimen has been evaluated. During 1989-2001,600 kidney transplantations has been performed in our center, 105 of them has been followed up 1-10 years (mean 5 years). All patients received cyclosporine A (CsA), cellcept or AZA and maintenance prednisolone. But with the onset of GI complication or leukopenia, some alternations in Immunosuppressive regimen were considered and patients were divided to 4 groups. Group 1 (31 patients) developed severe, resistant leukopenia and the AZA was discontinued permanently. Group 2 (38 patients) developed leukopenia with dose of 3 mg/kg. The AZA was reduced to 1 mg/kg. In group 3, all 26 patients received AZA with the dose of 3 mg/kg without any leukopenia. In group 4 (10 patients) AZA was replaced by mycophenolate mofetil (MMF) 2 gr daily after onset of leukopenia. Data were analyzed using the SAS system (Ver 6.12). Mean creatinine level was 1.32, 1.24, 1.31, 1.38 mg/dl in each group respectively. Acute rejection was reported to be 7,2,3,2 in each group respectively. Using Analysis of Variance (ANOVA) and nonparametric methods of comparison; no significant difference were found in mean creatinine level of all groups (P=0.77 and 0.65). The relationship between acute rejection and groups were analyzed by using the discrete analysis methods such as exact and chi square (type) methods and no significant association was observed (P=0.18). When studying chronic rejection, there was, however, a significant difference only between groups 1 and 2 in long term (P<0.05). But the incidence of graft loss was not significantly different in all groups during the first year after transplantation. Minimal dose of AZA (1 mg/kg) along with CsA and prednisolone can prevent induction of leukopenia wihtout any significant rise in incidence of acute rejection and graft failure as compared to standard regimen and CsA, MMF and prednisolone protocol. Also CsA and prednisolone alone are only recommended during the first year after transplantation.