A series of glycolide/epsilon-caprolactone copolymers were compression molded and allowed to degrade in a pH 7.4 phosphate buffer at 37 degreesC. Degradation was monitored by various analytical techniques such as H-1 NMR, X-ray diffraction, DSC, CZE, ESI-MS, and inherent viscosity measurements. The results show that the degradation rate depends not only on the copolymer composition but also on its chain microstructure. Generally, copolymers with a higher C-G bond content or a higher degree of randomness exhibit higher degradation rates. Sequences with odd numbers of glycolyl units such as -CGC- and -CGGGC-, which result from the second mode transesterification, appear more resistant to hydrolysis. As a consequence, degradation residues obtained at the later stages of degradation are mainly composed of long glycolyl and caproyl sequences linked by -CGC- and -CGGGC- ones. The degradation rate of the copolymers depends also on the degree of crystallinity of each component which is related to the block length. The caproyl component can be preferentially degraded if it is in the amorphous state and the glycolyl component is semicrystalline.