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Objectives: Tacrolimus (FK506) is a potent immunosuppressive drug used for prevention of rejection following transplantation. Several methods including immunoassays have been used for monitoring tacrolimus levels. The purpose of the present study was to compare the effects of various hematological parameters on whole blood tacrolimus concentrations which were measured with two different analytical methods, namely the microparticle enzyme immunoassay (MEIA II) and enzyme multiplied immunoassay technique (EMIT)., Design and Methods: The effects of hematological variables, namely hematocrit (Htc), hemoglobin (Hb), red blood cell (RBC), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), red cell distribution width (RDW) and platelet (PLT) counts on tacrolimus concentrations (n = 2430 measurements) measured with EMIT (n = 1171) and MEIA II (n = 1259) methods in whole blood samples from kidney or liver or combined kidney-pancreas transplant patients (n = 162) during a 2-year post-transplantation period were compared., Results: The whole blood tacrolimus concentrations measured with MEIA II method were affected much more significantly by hematological parameters than those measured with EMIT method. In MEIA II method, RDW (r = 0.479, P < 0.01) showed a stronger correlation with tacrolimus concentration than Htc (r = -0.239, P < 0.01) in all patients. A negative significant correlation (r = -0.468, P < 0.01) was also observed between the Htc and tacrolimus concentration in patients with Htc values < or =25% in MEIA II method., Conclusions: The results of the present study suggest that EMIT method might be preferred to MEIA II in determination of whole blood tacrolimus concentrations in anemic transplant patients. For better therapeutic drug monitoring, physicians should be aware of these assay differences. Evaluation of hematologic factors that affect the whole blood concentrations of tacrolimus may be helpful in deciding the dosage of this drug.