Assess the relationship between Cyclosporine (CsA) whole blood maximum concentration (Cmax), lymphocyte maximum level (LTmL) and the degree of its bioactivity reflected by the total lymphocyte count (LC) in stable kidney transplant patients. A total of 182 blood samples were obtained from 32 patients at different CsA dosages during the first 6 months post-transplantation. Cmax, LTmL and total LC were determined simultaneously. Cmax and LTmL were compared among each other and according to CsA dosage and the relationships between these three parameters (Cmax, LTmL and dose) and the total LC were analysed. Cmax failed to correlate with LTmL (R2=0.001). This was related to a significant inter-patients variability in these parameters (up to 15-20 fold) within each CsA dosage and the consequent poor relationship of both Cmax and LTmL with CsA dose (R2=0.054 and R2=0.09), respectively. Similarly, the total LC exhibited a striking difference among patients when compared in relation to the CsA dosage (R2=0.0003) and failed to correlate with Cmax (R2=0.05). In contrast, LTmL strongly correlated (R2=0.48) with the total LC in a exponential manner. Our results clearly demonstrate a poor relationship between CsA Cmax and both CsA lymphocyte content (LTmL) and immune responsiveness. Given its strong correlation with the LC, LTmL may offer a new alternative for CsA monitoring at its site of action in renal transplantation.