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The binding of docetaxel to human plasma proteins was studied by ultrafiltration at 37°C and pH 7.4. Docetaxel was extensively (> 98%) plasma protein bound. At clinically relevant concentrations (1–5 μg/ml), the plasma binding was concentration-independent. Lipoproteins, alpha₁-acid glycoprotein and albumin were the main carriers of docetaxel in plasma, and owing to the high interindividual variability of alpha₁-acid glycoprotein plasma concentration, particularly in cancer, it was concluded that alpha₁-acid glycoprotein should be the main determinant of docetaxel plasma binding variability. Drugs potentially coadministered with docetaxel (cisplatin, dexamethasone, doxorubicin, etoposide, vinblastine) did not modify the plasma binding of docetaxel. In blood, docetaxel was found to be mainly located in the plasma compartment (less than 15% associated to erythrocytes).