Intragastric immunization may lead to the induction of antibodies in the secretory immune system including saliva. The antibody response is usually short-lived. The objectives of this study were to see whether oral immunization with biodegradable microparticles containing antigen might lead to enhanced mucosal responses. Ovalbumin (OVA) was entrapped in a novel antigen delivery system comprising poly (D,L-lactide-co-glycolide) (PLGA) microparticles. Salivary IgA and serum IgG responses after three daily oral immunizations in BALB/c mice were assayed by ELISA at weekly intervals and compared with those to soluble antigen. Low levels of salivary IgA antibodies were detected at Weeks 2 and 3 in both groups and no significant differences were found. After a secondary series of intragastric immunizations at Week 4, marked differences were apparent between the groups. The mean salivary IgA titre at Week 6 was 959 +/- 494 U compared with 30 +/- 5 in the soluble OVA group (P less than 0.0001). Significant differences were still apparent at Weeks 7-8 through the value was falling. Serum IgG antibodies were detectable and were significantly greater in the particle group (at Weeks 4 and 8) than in controls (P less than 0.001). These results suggest that microparticles are taken up by antigen-presenting cells in Peyer's patches, then slowly degrade in vivo and release entrapped antigens, and thus can function as potent antigen delivery systems giving rise to both mucosal and systemic responses. Microparticles have considerable potential as a controlled released antigen delivery system for the induction of longer-term immune responses at mucosal surfaces.