To monitor prospectively and simultaneously the De novo CsA-treated kidney transplant patients with the time average Cyclosporine-A (CsA) maximum lymphocyte level (LT1:30L) and its corresponding whole blood level (BT1:30L). CsA LT1:30L and BT1:30L were determined simultaneously at one and a half hour after drug ingestion in 37 patients at 1, 2, and 3 months after kidney transplantation. Patients with biopsy-proven acute rejection (REJ+ group) were compared to those without rejection (REJ- group) in relation to LT1:30L, BT1:30L and total lymphocyte count (TLC). Five patients (13.5%) experienced acute rejection during the study period. LT1:30L were significantly lower in the REJ+ group (51±12, 52±8 and 45±10 pg/lymphocyte at 1, 2, and 3 months as compared to the REJ- (82 ± 58, 77 ± 36 and 73 ± 35 pg/lymphocyte, P=0.005, P=0.01 and P=0.01) respectively, despite similar BT1:30L (2031 ± 350, 1679 ± 562 and 1093 ± 193 ng/mL vs. 2112 ± 1023, 1939 ± 647 and 1591 ± 504 ng/mL and similar CsA dosages. TLC were significantly higher in the REJ+ group as compared to the REJ- one during the first 2 months (0.00236 ± 0.00052 x 109/L vs. 0.00174 ± 0.001 x 109/L and 0.00247 ± 0.00029 x 109/L vs. 0.00155 ±0.00093, P=0.05 and P=0.006) respectively and similar at the third month (0.00167 ± 0.00025 x 109/L vs. 0.0014 ±0.00059 x 109/L, P=NS). Monthly mean serum creatinine levels were significantly better in the REJ- group. Similar findings were observed when all monitoring parameters were compared at the time of graft biopsy. In conclusions, These results confirm our previous observations on the strong association between acute rejection and low CsA intra-cellular levels irrespective of whole blood concentrations. CsA LT1:30L seems to offer a simplified and more reliable alternative than does BT1:30L for cyclosporine-A monitoring in kidney transplant patients.