Enteric infections induce a response of circulating pathogen-specific antibody-secreting cells (ASC). The expression of homing receptors (HRs) on these cells was studied in patients with diarrhea caused by Vibrio cholerae in Bangladesh, an area in which cholera is endemic. The gut HR, alpha4beta7, was expressed by approximately 80% of the ASC, indicating mucosal homing of these cells. However, the peripheral lymph node HR, L-selectin, was also expressed by approximately 80% of the ASC specific to either cholera toxin or O antigen. In earlier findings after oral immunization in nonendemic areas, alpha4beta7 has been expressed by approximately 100% and L-selectin by approximately 50% of the ASC. In comparison, the present data speak for a more systemic targeting of the immune response associated with long-lasting immunity in an endemic area. The results thus provide insight for the continued development and evaluation of vaccines.