Much may be learnt about the suppression of autoimmunity using animal models of transplantation. The interaction between CD40 on B cells and CD40 ligand expressed predominantly by activated CD4+ T cells plays an important role in the development of the humoral immune response and the induction of peripheral tolerance. Monoclonal antibodies against CD4 and CD8 have been shown to induce CD4-regulated tolerance of mismatched transplanted tissues in rodents. These regulatory CD4+ cells also prevent the rejection of grafts, which co-express the antigens to which tolerance has been induced along with third party antigens. This phenomenon is known as linked suppression. The CD40/CD40L interaction is also an attractive target for immunotherapy, with the objective of inducing transplantation tolerance or the control of autoimmunity. To investigate whether nonlytic mAbs against CD40L induce tolerance to minor alloantigens in murine skin grafts, and whether linked suppression occurs in this system.