The in vitro controlled release kinetics of human immunoglobulin G (IgG) of different loadings from microspheres of the biodegradable polymers poly(L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) were investigated. The microspheres were prepared by a double-emulsion technique. The release profiles exhibited an initial burst followed by a period of slow release, with PLA microspheres showing a faster rate of release than PLGA microspheres. The release rate increased with an increase in drug loading. Scanning electron microscopy (SEM) observations revealed wide differences in the morphology of microspheres made from different polymers. Drug loading had no significant effect on the morphology of the microspheres. Laser scanning confocal micrographs demonstrated a homogeneous drug distribution within the microspheres. Results from SEM and mass loss studies revealed no significant extent of polymer erosion after 50 days of release. Modeling studies within the first 50 days of incubation suggested that the mechanisms of drug release were mainly diffusion- and dissolultion-controlled.