Sirolimus (RAPA) blood monitoring is considered as an essential pre requisite to the use of this novel immunosuppressant. For the time being there is no readily available recognized technique for a radioimmuno assay e.g. IMX determination of RAPA. Instead, reference centers using HPLC methods (UV) have been designated to provide RAPA users with levels supposed to guide them in the prescription of the drug. RAPA through level (T0) is said to be a valid representative of RAPA AUC (Area Under the Curve) and has been advocated as the best criterion for RAPA dosing. We report our single center experience with the use of RAPA T0 monitoring in 22 patients receiving RAPA (2-5 mg/day) in association with either MMF (16 patients) or AZA (6 patients) without calcineurin inhibitors. In our experience when RAPA was used alone, reaching a T0 of 10-15 ng/ml has not provided a sufficient protection against acute rejection. Eighteen per cent had biopsy-proven rejections, the rest did not drop their serum creatinine, while many RAPA toxic effects were noted. RAPA levels one hour after drug intake (T1) correlated better (R=0.54) than T0 (R=0.01) with the RAPA dose. RAPA whole blood levels on the other hand were adversely affected by higher hematocrit (R=0.7). T0 Cell Cept levels showed a tendency to rise at higher doses of RAPA. In conclusion, RAPA whole blood T0 levels as used presently did not prove to be a useful guide to the use of the drug. A more available technique, using T1 rather than T0 and measuring drug levels at one of RAPA’s major sites of action e.g. the lymphocytes, might be the answer.