Transfer of parental strain T lymphocytes into F₁ hybrid rats differing with respect to gene products of the major histocompatibility complex (MHC) causes a graft-versus-host (GvH) reaction. This reaction results from recognition of host allogeneic MHC gene products by specific clones of donor T cells¹. When given systemically in sufficient numbers, these donor T cells cause a progressive, generally fatal wasting syndrome, an early feature of which includes extensive splenomegaly^2,3. A more local, non-fatal GvH reaction, marked by extensive enlargement of the draining lymph nodes, ensues when donor T cells are administered via the footpad^4,5. Here, we demonstrate that cells derived from the enlarged draining lymph nodes of A/B F₁ animals undergoing local GvH disease caused by donor AT cells contain a subpopulation of host-derived killer T-cell precursors which can be activated to lyse specific blast cells, derived from mixed lymphocyte culture (MLC), reactive to host MHC^b alloantigens. These ‘anti-idiotypic’ cytolytic T cells lyse A anti-MHC^b MLC blasts, and also, they lyse anti-MHC^b MLC blasts from MHC different, third party rat strains.