Five healthy female adult volunteers were intranasally immunized twice (7-day interval) with 250 μg of a crude glucosyltransferase (GTF) preparation from Streptococcus mutans in liposomes. Parotid saliva, nasal wash, and serum were collected prior to and at weekly intervals for 6 weeks following the first immunization for analysis of anti-GTF activity by enzyme-linked immunosorbent assay. The levels of IgA1 anti-GTF activity increased in the nasal wash from all five individuals after immunization. Increases in salivary IgA1 and IgA2 anti-GTF activities were observed to a lesser extent. Increased serum IgM and IgA (but not IgG) anti-GTF activities were seen in immunized subjects. Nasal immunization with a dehydrated liposome-protein vaccine was effective in inducing an apparent secretory IgA antibody response, which was primarily of the IgA1 subclass. These results provide the first evidence of the effective use of a nasal liposome-protein vaccine in humans.