Ovalbumin (OVA) was entrapped in microparticles prepared from three different poly(lactide-co-glycolide) (PLG) polymers and the microparticles were administered subcutaneously to mice as a single dose. Two weeks after immunization, the serum IgG antibody response to OVA entrapped in microparticles was significantly greater than the response to soluble OVA. The response to OVA entrapped in microparticles peaked at week 10 and remained high for the full 1-year duration of the study. In a second study, the effect of particle size on the immunogenicity of PLG microparticles with entrapped OVA was assessed. Following booster immunizations in mice, microparticles of 1.5 microns were significantly more immunogenic than microparticles of 72.6 microns. Furthermore, although enhanced serum IgG responses were induced by immunization with OVA adsorbed to microparticles (1.0 microns), entrapment of the OVA in microparticles (1.5 microns) resulted in significantly better responses.