Experiments are described for T‐independent polyclonal activation of B cells in vitro by the immunoglobulin binding substance (IBS) from the granary weevil. The affinity‐chromatographically purified IBS was used. IBS is a heat‐, alkali‐ and acid‐stable glucopeptide which is characterized by non‐specific immunoglobulin binding lo the Fab fragment. The purified IBS consists of three polymer homologues whose molecular weights are 12–14,000, 25–30,000 and more than 150,000 Da. IBS did not stimulate DNA synthesis by murine T cells, macrophages or plasma cells whereas it did stimulate that by mature B cells without any help from T cells or macrophages, IBS also stimulated both in vitro IgG production by spleen cells and in vitro sensitization of spleen cells by sheep red cells (SRBC). IBS was found to stimulate DNA synthesis by B cells mediated by binding to surface immunoglobulins of B cells. IBS is thought to be a useful amplifier for inducing human hybridomas and a valuable tool for examining mature B cells, both diagnostically and