Oral immunisation may elicit both systemic and mucosal immunity. Antibodies directed to a portion (residues 816-1213) of a cell surface adhesin termed streptococcal antigen I/II (SA I/II) of Streptococcus mutans prevent colonisation of this bacterium in vivo. This polypeptide is highly immunogenic in mice and is immunodominant in naturally sensitised humans. In this study, the effects of immunisation by different routes and of adjuvant on T and B cell epitope recognition were investigated. The recombinant polypeptide comprising residues 816-1213 of SA I/II was administered to groups of SJL mice intraperitoneally, subcutaneously or orally. For systemic immunisation, incomplete Freund's adjuvant was used, whereas for oral immunisation the antigen was coupled to the cholera toxin B subunit. The hierarchy of T and B cell epitope recognition differed significantly following different routes of immunisation. These differences in T and B cell responses may be accounted for by extracellular protease activity and processing by antigen presenting cells at the sites of immunisation. Furthermore, epitope recognition may be critical if the immune response elicited by a vaccine must be directed specifically to functional determinants within an antigen. This study emphasises the importance of route of immunisation in vaccine development.