In vitro human serum protein binding studies, telithromycin (TEL) was moderately bound to serum proteins. The percentage binding was 60-70% around Cmax. Two binding coefficient (Nka) were estimated in all of tested serum, and these evidences suggest that albumin and α1-acid glycoprotein could be the main protein responsible for the binding of TEL. Binding of TEL to lipoprotein (HDL, LDL and VLDL), γ-globulin and isolated erythrocytes were weak. The samples from an overseas phase I repeated dose study were examined for the in vivo protein binding rate by a centrifugal ultrafiltration method. The rate of free form of TEL ranged from 37.1% to 46.5% at the plasma concentrations of TEL ranging from 0.116 to 3.175 mg/L, the results were similar to those obtained in vitro. Among the overseas studies conducted in special populations, additionally, the protein binding rates in the elderly and the patients with hepatic disorder were similar to those obtained in healthy adults.