Seven healthy adult volunteers each ingested an enteric-coated capsule containing 500 micrograms of Streptococcus mutans glucosyltransferase (GTF) in dehydrated liposomes for 3 consecutive days. The immunization regimen was repeated 28 days later. Parotid saliva and plasma were collected prior to and at a weekly interval for 8 weeks following the first immunization for analysis of anti-GTF activity by enzyme-linked immunosorbent assay. The levels of immunoglobulin A1 (IgA1) and IgA2 anti-GTF activities increased in the parotid saliva from 5 of 7 individuals after immunization. Increases in the mean level of IgA1 and IgA2 anti-GTF responses peaked on day 35 (77% and 175% increase over baseline, respectively), although variation was noted in the kinetics and subclass of responses between individuals. No salivary IgG or IgM responses were observed. Low plasma IgM, IgG and IgA anti-GTF responses were seen in immunized subjects. Oral immunization with a dehydrated liposome-protein vaccine was effective in inducing a secretory IgA antibody response, which was primarily of the IgA2 subclass. These results provide the first evidence for the use an oral dehydrated liposome-protein vaccine in humans.