A well-defined amphiphilic block copolymer was synthesized by the coupling of carboxyl-terminated methoxy poly(ethylene glycol) (MPEG) with a hydroxyl-terminated octamer of glycolic acid, which was obtained by a stepwise synthetic procedure with the end-group protection and deprotection. The block copolymer had a polydispersity index (PDI) of 1.01, as determined by gel permeation chromatography. It was further coupled to paclitaxel to form a prodrug of paclitaxel. The paclitaxel content in the prodrug was about 10%, and its PDI was 1.02. The antitumor activity of the conjugate against human lung carcinoma A549 cells was evaluated by mitochondrial dehydrogenase (MTT) assay. The results show that paclitaxel could be released from the conjugate without losing cytotoxicity. Therefore, the well-defined amphiphilic block copolymer from MPEG and oligomer of glycolic acid could potentially provide novel opportunities to obtain reproducible pharmacokinetic behavior in the design of a drug-delivery system. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 122: 758-766, 2011