The Fc receptor for IgA and IgM (Fcalpha/muR) is of particular interest because it can bind antibodies of both IgM and IgA isotypes and thus may play a pivotal role in systemic and mucosal immunity. Using IgM and IgA ligands and newly generated Fcalpha/muR specific monoclonal antibodies we have defined biochemical features and cellular distribution of the human Fcalpha/muR. Both recombinant and native forms of human Fcalpha/muR are expressed on the cell surface as remarkably stable homodimeric transmembrane glycoproteins that can bind specifically polymeric IgM or IgA. The only human B cells to express Fcalpha/muR, albeit at very low levels, are found in the pre-germinal center subpopulation defined by the IgD+/CD38+ phenotype. Hence the expression pattern differs from that of the mouse wherein Fcalpha/muR is expressed by both circulating and resident B cell populations. Significantly, the predominant cell type expressing the Fcalpha/muR in humans is the follicular dendritic cell of germinal centers. The Fcalpha/muR may thus function in antigen presentation and B cell selection in the germinal center response.