Background: Immune protection against cholera infection is probably mediated in part by locally produced, intestinal secretory IgA (sIgA) antibodies. We study the kinetics of intestinal (sIgA) and systemic (serum IgG) antitoxin antibody responses after immunization with whole-cell/recombinant B subunit oral cholera vaccine (WC/rBS) in U.S. travelers to Mexico and Mexican volunteers. Methods: Two doses of WC/rBS were administered 10 days apart to ten U.S. adults, newly arrived in Mexico, and 18 Mexican nationals. Serum IgG and intestinal secretory IgA (sIgA) antibodies to the B subunit of cholera toxin were measured from day 0 to day 21 by a direct enzyme-linked immunosorbent assay (ELISA). Results: Positive serum IgG responses to vaccination were detected in 80% of U.S. adults and in 59% of Mexican adults. All volunteers, regardless of nationality, developed a positive sIgA antibody response to WC/rBS. No differences were observed between U.S. and Mexican volunteers in the magnitude and kinetics of serum IgG responses. We recorded differences in the kinetics of sIgA antibody, with early and late peak sIgA antitoxin responses demonstrated in the Mexican and U.S. volunteer groups, respectively. Although the presence or absence of antitoxin sIgA antibodies prevaccination (sIgA titer > 1:4) did not interfere with the final postimmunization magnitude of the antibody responses (sIgA measurements days 14 and 21), the initial measurement curves showed differences (sIgA measurements days 0 and 3). Conclusions: The WC/rBS vaccine stimulated antitoxin antibody formation both in serum and locally in the intestine. The presence or absence of specific sIgA antibodies prevaccination did not seem to interfere with the magnitude of the antibody responses postvaccination (days 14, 21). The measurement of sIgA responses in fecal extracts appears to provide a simple and sensitive method to assess the intestinal immune response to orally administered vaccines.