Studies on intestinal immunity in animals have suggested that lymphocytes, after sensitization in Peyer's patches and maturation in regional lymph nodes, home via the circulation to the intestinal wall, where they secrete antibodies into the lumen. To detect such homing cells in the blood of human volunteers given oral, attenuated Salmonella typhi vaccine, we used the solid-phase enzyme-linked immunospot assay for S. typhi-specific antibody-secreting cells (ASCs). ASCs were found in eight of 10 individuals after the third postvaccination day, peaked in level on day 7, and were undetectable on day 14. Of the cells secreting specific immunoglobulin, approximately 62% produced IgA, 32% IgM, and 6% IgG. Antibodies could not be demonstrated in serum, saliva, or feces. This technique might give an opportunity to follow the response to antigens entering the body via mucous membranes. It will be of interest to correlate these findings with protection against diseases after peroral vaccination.