We aimed to determine the temporal variation of the time average Cyclosporine-A (CsA) maximum lymphocyte level (LTAML) in stable rejection-free De novo kidney transplant patients. Time average maximum lymphocyte level (LT1:30L) and whole blood level (BT1:30L) were determined simultaneously at one and a half hour after drug ingestion in 32 CsA-treated patients with stable graft function. A total of 149 blood samples were obtained at 0.5, 1, 2, 3, 6, 12 and 24 months post-transplantation. CsA LT1:30L and BT1:30L were compared retrospectively among each other and in relation to the total lymphocyte count (TLC) and dosage. Mean CsA LT1:30L and BT1:30L at 0.5, 1, 2, 3 , 6, 12 and 24 months were 104.6, 82.2, 77.3, 73.7, 59.2, 61.2, 49.2 pg/lymphocyte and 2096.5, 2112.4, 1838.5, 1591.3, 1220.8, 1237.8, 1142.2 ng/ml, respectively. Mean TLC and serum creatinine remained quiet stable ranging between 1407 to 1800 lymphocyte/ml and 0.8 to 1.1 mg/dl, respectively, throughout the study period. Mean CsA dosage were 4.3, 3.5, 3.1 and 2.5 mg/Kg at 3, 6, 12 and 24 months post-transplantation. CsA BT1:30L failed to correlate with LT1:30L (R2 = 0.026) and TLC (R2 = 0.048). Similarly, CsA LT1:30L correlated poorly with dosage (R2 = 0.082). This was related to significant inter-patients variability in the LT1:30L (up to 12 fold) within each CsA dosage. In contrast, LT1:30L exhibited a significant exponential relationship with TLC (R2 = 0.40). In conclusion, ur results clearly confirm our previous findings on the poor association between CsA intra-cellular level and CsA dosage, whole blood concentration and the TLC as an indicator of the immune state. In addition, they establish new guidelines which are in agreement with our previous observations, for a simplified safe LTAML for CsA therapy monitoring during the first 2 years post-transplantation.