In this study, we have examined the feasibility of immunisation against measles with plasmid DNA administered by the oral route. After the oral administration, in two 50 microg doses, of poly(DL-lactide-co-glycolide) (PLGA)-encapsulated DNA expressing measles virus nucleoprotein, increasing titres of N-specific serum IgG antibodies were observed in three of ten C3H/He mice over a period of three months. In comparison, oral vaccination of mice with a replication-defective recombinant adenovirus expressing the same transgene induced serum IgG in all animals tested. We also obtained preliminary indication of adjuvant-like activity of PLGA particles when coadministered intraperitoneally (i.p.) with naked plasmid DNA. These experiments demonstrate that oral delivery of either PLGA-encapsulated plasmid DNA or viral vectored DNA is capable of eliciting strong immune responses in mice. We propose that oral administration of biodegradable microparticles offers a novel strategy for future vaccine design for the safe delivery of DNA to mucosal surfaces.