Poly(lactic acid)s (PLA) were grafted to both ends of Pluronic F127 (PEO-PPO-PEO) to produce novel amphiphilic PLA-F127-PLA block copolymers. The hydrolytic degradation of PLA-F127-PLA block copolymers in phosphate buffered saline (PBS) (pH 7.4) solution at 37 degreesC was studied using a combination of physical techniques, such as dynamic light scattering (DLS), transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), and gel permeation chromatography (GPC). it was found that the morphologies and particle size of PLAF127-23 nanoparticles changed dramatically because of the initial rapid degradation of PLA blocks. The morphology of the microstructure transformed from the regular onionlike vesicles to large compound vesicles. With increasing time, the degradation rate of LA-LA linkage was reduced, and the degradation mainly occurred at the interface of F127 and PLA blocks. The morphologies of PLAF127-23 nanoparticles changed from the regular larger compound vesicles to irregular compound vesicles, and to regular large compound vesicles as degradation progresses. Accordingly the particle size of PLAF127-23 nanoparticles decreased initially and remained constant for a certain time period, and it then increased again.