Compare the clinical relevance of two distinct immunosuppression therapy monitoring techniques Tacrolimus (TAC) lymphocyte (LT₀L) and blood trough levels (BT₀L) in Denovo kidney transplant patients. TAC LT₀L and BT₀L were determined simultaneously in patients with biopsy-proven graft dysfunction (6) and in patients (15) with normal graft function (NORM). Clinical outcome and lymphocyte count were compared according to TAC LT₀L, BT₀L, and dosage.Rejecting (REJ) patients (9%) exhibited lower TAC LT0L than the NORM (2.3±0.7 pg/Lc vs 4.6±3.1 pg/Lc, P<.003) and had comparable values to those (2.0±2.1 pg/Lc) with nephrotoxicity (TOX) (23%), despite similar TAC BT0L (12.0±3.8 µg/mL, 12.8±4.7 µg/mL and 11.5±2.5 µg/mL) respectively. TAC dosage was higher in the REJ group (0.21±0.03 mg/Kg) as compared to either NORM (0.17 ± 0.04 mg/Kg, P<.02) or TOX (0.18±0.05 mg/Kg, P<.04) one. NORM patients had lower lymphocyte count (0.000887±675 x 109/L) when compared to the REJ (0.001331±390 x 109/L, P<.05) and TOX (0.002185±935 x 109/L, P<.001) ones. TAC LT₀L but not TAC BT0L strongly correlated with the lymphocyte count (R2=0.99, P ) in an exponential fashion. These results suggest that TAC LT₀L exhibits a stronger clinical relevance than BT0L, mainly with acute rejection and lymphocyte count. Neither parameter correlated with nephrotoxicity. TAC LT₀L may offer a better alternative for TAC therapy monitoring in kidney transplantation.