The potential to generate both a systemic and local immune response makes the mucosal system an attractive site for immunization. However, mucosal administration of protein and peptide antigens generally results in a poor immune response. Successful mucosal vaccination is therefore largely dependent on the development of effective mucosal adjuvants. In this study we have examined the effect of mucosal administration of tetanus toxoid (TT) in the presence of a non-ionic block copolymer, Pluronic F127 (F127), with chitosan or lysophosphatidylcholine (LPC) on the systemic and mucosal immune response. Balb/c mice, immunized intraperitoneally (i.p.) with TT and boosted intranasally (i.n.) with TT in F127/chitosan, demonstrated a significant enhancement in the systemic anti-TT antibody response compared to mice boosted i.n. with TT in PBS or mice boosted i.n. with TT in F127/LPC. We determined the antigen specific IgA response in the nasal and lung washes of these animals and found a significant increase in anti-TT mucosal IgA response in the group boosted with TT in F127/chitosan. Similarly, mice immunized and boosted i.n. with TT in F127/chitosan had a significant enhancement of their systemic anti-TT IgG and mucosal IgA antibody responses compared to the animals immunized and boosted i.n. with TT in PBS or TT in F127/LPC. The results of these studies suggest that F127/chitosan represents a novel mucosal vaccine delivery system, consisting of two components, that appear to exert an additive or synergistic effect on the immune response.