Purified polysaccharide antigens are often poorly immunogenic, especially when given by the oral route. However, it has been shown in experimental animals that liposomes can greatly increase the immunogenicity of certain polysaccharide antigens. Here we report the induction of immune responses in humans to an oral vaccine consisting of liposomes containing purified serotype carbohydrate antigen of Streptococcus mutans, the primary etiological agent of dental caries. Four volunteer subjects swallowed enteric coated gelatin capsules containing liposomal-antigen for seven consecutive days. Pre- and post-immunization samples of saliva and plasma were analyzed for antibody activity to S. mutans carbohydrate by ELISA. Salivary anticarbohydrate IgA responses were detected in all four subjects between day 21 and day 32. Upon second and third immunizations, subjects experienced salivary responses earlier than following the first immunization. Early (day 4-7) plasma IgA responses to the carbohydrate were found in three subjects which consisted of both polymeric and monomeric forms. Variable levels of plasma IgG anti-carbohydrate antibody activity were seen in three individuals. These results show that orally administered liposomal-S. mutans serotype carbohydrate antigen induces a salivary IgA response in humans and provides evidence for the efficacy of liposomal antigen delivery system in the induction of a protective mucosal immune response against microbial pathogens.