The site of antigen encounter influences the Ig-distribution and homing potentials of circulating antibody-secreting cells (ASC) induced. After oral antigen administration, the majority ASC secrete the mucosal Ig-isotype, IgA, and all of them express the gut homing receptor (HR), alpha 4 beta 7, thus implying mucosal homing of these cells. Parenteral protein vaccine induces an IgG-dominated response with a low proportion of alpha 4 beta 7 expressing cells. However, a polysaccharide vaccine, even if administered parenterally, elicits an IgA-dominated response, hence suggesting homing to the mucosa. In order to study the influence of the nature of the antigen on the targeting of the ASC response, the present work compares the homing potentials of circulating ASC in humans after administration of an oral Salmonella Typhi Ty21a vaccine (antigen studied: O-9,12 polysaccharide), an oral recombinant cholera vaccine (antigen studied: cholera toxin B-subunit, CTB protein), a parenteral pneumococcal vaccine (antigen studied: Pnc capsular polysaccharide 19F) or a parenteral tetanus toxoid vaccine (antigen studied: TT protein). alpha 4 beta 7 was expressed on a higher proportion of ASC induced by oral O-9,12 (99%) and CTB (99%) than by parenteral Pnc (70%) or TT (63%). L-selectin, the peripheral lymph node HR, was expressed on a smaller proportion of ASC induced by O-9,12 (37%) or CTB (43%) than of those induced by Pnc (78%) or TT (81%). The results imply that even if the nature of the antigen has a profound effect on the Ig-distribution of the ASC response, it does not seem to influence the targeting of the response.