The induction of protective immunity stemming from vaccines delivered by mucosal routes is dependent on the development of safe and effective mucosal adjuvants. The immunostimulant monophosphoryl lipid A (MPL(R)) was evaluated for its ability to enhance both systemic and mucosal immunity to three distinct antigens. Vaccines formulated with MPL(R) and hepatitis B surface antigen, tetanus toxoid or influenza antigens were administered by intranasal delivery to mice. In each case the vaccines formulated with MPL(R) resulted in enhanced IgA titers from mucosal samples. Enhanced IgA concentrations were detected in samples from both local and distal mucosal sites. In addition, the MPL(R) formulated vaccines induced systemic immunity characteristic of a Th1-type of response. Serum IgG2a antibody titers were elevated and cytotoxic T cell activity was enhanced.