Polyclonal antithymocyte globulins (AThG) are a subset of antilymphocyte antibody preparations derived from the sera of rabbits or horses immunized with unfractionated cells isolated from pediatric human thymi. In vivo, AThG preparations have been used to successfully treat antibody mediated rejection in kidney transplant recipients. In vitro, AThG can induce apoptosis of naïve and memory B cells and terminally differentiated plasma cells. The presence of B-cell reactive antibodies in AThG results from a thymic inoculum containing a significant percentage of CD20(+) B cells and CD138(+) plasma cells. In this paper, the experimental and clinical evidence supporting the B-cell activity of AThG preparations, and their mechanisms of action, are reviewed.