This paper describes the conditions of preparation of poly(lactide-coglycolide) microspheres with a mean diameter lower than 10 μm obtained by a (w1/o)w2 emulsion solvent evaporation method. Different parameters influencing respectively the size of the inner emulsion and the diameter of the microspheres were determined. V3 BRU, which is a specific immunogenic fraction from GP120 of HIV, was encapsulated in those microspheres. The entrapment efficiency was shown to be superior to that of microspheres prepared according to the single emulsion solvent evaporation method. Electron microscopy observations demonstrated the presence within the microspheres of globules corresponding to the w / o initial inner emulsion in which the peptide was dissolved in the aqueous phase. Analysis of the release kinetics was carried out in phosphate buffer (PBS), in artificial gastric and intestinal medium. V3 BRU release in PBS was slow, reaching a plateau at 24 h corresponding to 25% of drug release. In addition, V3 BRU was not released in gastric medium within 4 h whereas under the same time conditions, 60% of the drug was released in the presence of intestinal medium. These results open up interesting prospects for the use of these microspheres as an oral adjuvant for HIV vaccination.