Biodegradable and biocompatible microspheres have been investigated for their usefulness as a vaccine delivery system for both parenteral and enteral immunization. Microspheres composed of poly(DL-lactide-co-glycolide) which contained a toxoid vaccine of Staphylococcal enterotoxin B were found to strongly potentiate the circulating anti-toxin antibody response following intraperitoneal injection. Following oral administration, microspheres less than 10 microns in diameter were specifically taken up into the Peyer's patches of the gut-associated lymphoid tissue, where those greater than or equal to 5 microns remained fixed for an extended period. Microspheres less than 5 microns were disseminated within macrophages to the mesenteric lymph nodes, blood circulation and spleen. Oral immunization with enterotoxoid-containing microspheres induced circulating toxin-specific antibodies and a concurrent secretory IgA anti-toxin response in saliva, gut wash fluids and bronchial-alveolar wash (BAW) fluids. In contrast, soluble enterotoxoid was completely ineffective as an oral immunogen.