The in vitro degradation behaviour of a wide range of poly(D,L-lactic-co-glycolic acid) (PLGA) has been examined in terms of degree of degradation and morphological change during an incubation period of up to 53 d. Gel permeation chromatography and differential scanning calorimetry were employed to characterize their degradation profiles. It was found that amorphous PLGA exhibited a transient multiple crystallization behaviour of D- or L-lactic acid oligomers during degradation. This indicated that the hydrolytic scission of ester bonds tends to primarily target the linkage between glycolic acid and D- or L-lactic acid or glycolic acid. In addition, two distinctive glass transition temperatures appeared when these crystallization phenomena occurred, suggesting the transient presence of fast and slowly eroding polymer domains within microspheres during the degradation. This study supports the heterogeneous bulk degradation for PLGA microspheres which has been proposed recently for a large specimen.