Intestinal M cells bear a receptor for secretory immunoglobulin A (IgA) (sIgA) facing the lumen of the epithelial surfaces. Cells bearing this receptor are also found throughout an experimental monolayer consisting of polarized Caco-2 cells, a colon adenocarcinoma cell line. The presence of antibodies (mainly sIgA) in the lumen of the small intestine led us to explore the participation of the sIgA receptor and antibodies in the interaction of Caco-2-associated M-like cells with the mucosal pathogen Vibrio cholerae. Here, we demonstrate that sIgA antibodies isolated from pooled healthy human colostrums, as well as IgG from pooled healthy human serum, can recognize V. cholerae. Furthermore, opsonization enhances M-like-cell transcytosis of V. cholerae strains. We also show that the cholera toxin (CT) receptor ganglioside GM(1) colocalizes with the sIgA receptor in cells of the epithelial monolayer. Both sIgA and IgG antibodies compete for the attachment of soluble CT subunit B to immobilized GM(1). Our results indicate that in this in vitro model system of intestinal epithelia, human sIgA and IgG contribute to the uptake of V. cholerae by M-like cells, probably through an interaction with GM(1). Our results support previous findings of others showing that sIgA can act as an endogenous adjuvant and that sIgA is important for the antigen-sampling function of M cells.