The intestinal immune response of volunteers given the oral vaccine Salmonella typhi Ty21a was assessed with a new immunoassay which measures specific antibody secretion by peripheral blood lymphocytes (PBL). Peak IgA, IgG, and IgM production by PBL occurred on day 7 after the start of vaccination. Peak antibody secretion by PBL occurred several days earlier than the serum antibody peak. All volunteers showed a specific PBL antibody response, but serum or intestinal immune responses, when demonstrable, were highly variable. Peak PBL IgA antibody response correlated with degree of rise in IgA antibody in serum (p = 0.00098) and the intestinal fluid (p = 0.0024). The assay is a useful means of measuring humoral immune response at a mucosal surface after local administration of antigen.