The optimal synthetic conditions of poly(lactic acid-co-glycolic acid) (PLGA) via melt copolycondensation directly from L-lactic acid (L-LA) and glycolic acid (GA) with a feed molar ratio of 50/50 are discussed; the important drug-delivery carrier PLGA50/50 is used as a special example. With reaction conditions of 165 degrees C and 70 Pa and with 0.5 wt % SnCl2 as the catalyst, 10 h of polymerization gave the L-PLGA50/50 with the biggest intrinsic viscosity ([eta]), 0.1993 dL/g. The optimal synthetic conditions were verified by the synthesis Of D,L-PLGA50/50 with D,L-lactic acid (D,L-LA) instead Of L-LA, but the biggest [eta] was 0.2382 dL/g. Under the same synthetic conditions with L-LA and D,L-LA as starting materials, serial PLGA with different molar feed ratios, including 100/0, 90/10, 70/30, 50/50, 30/70, 10/90, and 0/100, were synthesized via simple and practical direct melt copolycondensation, and their solubilities were investigated. When the glycolic acid feed molar percentage was equal to or more than 70%, solubilities in tetrahydrofuran and CHCl3 became worse, and some samples were even wholly insoluble. These biodegradable polymers were also systematically characterized with gel permeation chromatography, Fourier transform infrared spectroscopy, H-1-NMR spectroscopy, differential scanning calorimetry, and X-ray diffraction. PLGA synthesized from L-LA and D,L-LA had many differences in weight-average molecular weight (M-w), glass-transition temperature, crystallinity, and composition. When the molar feed ratio of LA to GA was 50/50, both the [eta] and M-w values Of D,L-PLGA were higher than those Of L-PLGA. With D,L-LA as the starting material, the structure of the PLGA copolymer was relatively simple, and its properties were apt to be controlled by its GA chain segment. When the feed molar percentage of the monomer (LA or GA) was more than or equal to 90%, the copolymer was apt to be crystalline, and the aptness was more obvious for the L-LA monomer. The composition percentage of GA in PLGA was not only higher than the feed molar percentage of GA, but also, the GA percentage in D,L-PLGA was higher than in L-PLGA. (c) 2005 Wiley Periodicals, Inc.