Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to ensure successful cognate interactions. Although cognate interactions between T cells and memory B cells (B mem) are essential for the secondary humoral immune responses, the chemokine response patterns of B mem cells are largely unknown. In contrast to naive B cells, this study shows that Ag-specific B mem cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. Although CCR6 appears be nonessential for the initial clonal expansion and maintenance of B mem, CCR6 is essential for the ability of B mem to respond to a recall response to their cognate Ag. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient B mem was revealed by immunohistological analysis with an altered distribution of CCR6-deficient B mem from the marginal and perifollicular to the follicular/germinal center area.