This chapter reviews studies performed with anti-immunoglobulin (anti-Ig) antibodies and outlines the state of knowledge about the relative direct and indirect roles of surface immunoglobulin (slg)-ligand interactions in the generation of an immune response; and differences in the roles played by B cell slgM and slgD in B cell activation. The use of anti-Ig antibodies in studies of B cell activation is predicated on the belief that the interaction between anti-Ig antibody and B cell slg has similar consequences on a polyclonal level to the interaction between an antigen and the slg of a B cell specific for that antigen. In vitro and in vivo studies with anti-Ig antibodies have demonstrated that these agents can rapidly induce changes in B cell surface receptor expression and stimulate these cells to enter the cell cycle and to synthesize DNA. Relatively high concentrations of soluble anti-Ig antibodies must be used to induce B cells to synthesize DNA.