Alloreactive B cells can contribute to graft rejection. Anti-CD154 treatment together with donor-specific transfusion (DST) results in the long-term survival of MHC-mismatched mouse heart grafts and inhibition of alloantibody production. To characterize the mechanism of B cell tolerance induced by the anti-CD154 and DST, we used 3-83Igi mice, on BALB/c (H-2K^d) background, that express a B cell receptor that reacts with MHC class I antigens H-2K^b. Transplanting C57BL/6 (H-2K^b) hearts into 3-83Igi mice, followed by tolerance induction, resulted in the peripheral deletion of mature but not immature 3-83 B cells. The sustained deletion of mature alloreactive B cells required the presence of the allograft and can be explained by the absence of T cell help.