Membrane immunoglobulin (Ig) on B cells plays a role in specifically focusing antigen onto the cell surface. An unresolved question is whether the Ig receptor itself has the capacity to deliver a signal to the B cell, and if so what is the mechanism of that signal. To explore these questions we have developed a monoclonal rat anti-mouse mu chain antibody (E4). In this study it is shown that protein A-Sepharose-purified monoclonal anti-mu chain antibody inhibits proliferation of normal B cells in vitro even at the single cell level. This effect was independent of Fc receptor interactions. Furthermore, E4 was shown to inhibit lipopolysaccharide-induced mitogenesis. These results provide evidence that interaction of antibody with only a single determinant on the Ig receptor can deliver a negative signal to the B cell.