BSA was entrapped in particles of different sizes (200, 500 and 1000 nm) prepared from poly(D,L-lactic-co-glycolic) acid by a double emulsion method. The particles were given, either intranasally, orally or subcutaneously, to Balb/c mice and the serum IgG, IgG1 and IgG2a response elicited was compared to that obtained by the subcutaneous administration of either free antigen, free antigen emulsified 1:1 with Freund's Complete Adjuvant (FCA), or free antigen administered with Al(OH)(3). The administration of 1000 nm particles generally elicited a higher serum IgG response than that obtained with the administration of 500 or 200 nm sized nanospheres, the immune response for 500 nm particles being similar than that obtained with 200 nm by the subcutaneous and the oral route, and higher by the intranasal route. PLGA nanoparticles can elicit serum IgG2a responses by the three routes studied. No significant differences on the serum IgG2a/IgG1 ratios were found after the subcutaneous, the oral and the intranasal administration of the different spheres but those were in general higher compared to the administration of either free antigen or free antigen adsorbed to alum. The route of administration influences the serum IgG2a/IgG1 ratio after the administration of free antigen, but not after the administration of the particles. Therefore, differences on the total serum IgG response induced by particles of different sizes do not result in differences on the IgG1 or IgG2a-type immune responses, suggesting that the antigen processing and presentation is similar in all cases tested for PLGA particles.