A systemic GVH reaction is initiated in F₁ hybrid rats by the i.v. injection of parental strain thoracic duct lymphocytes (TDL). It has previously been shown that some of the parental TDL react to transplantation antigen within 24 hours of injection by transformation into a large, pyroninophilic cell in the spleen, and to a lesser extent in the lymph nodes, of the recipient (1). However, the majority of parental strain lymphocytes continue to recirculate in the F₁ recipient and can be recovered by collecting thoracic duct lymph from the recipient for the first 36 hours after injection. It has recently been shown that parental strain lymphocytes which have migrated from blood to lymph in F₁ hybrid recipients are profoundly unresponsive against the recipient-type antigen in a graft-versus-host (GVH) assay (2). This unresponsiveness is specific since there is no decrease in the GVH activity of “filtered” lymphocytes against a third party allo-antigen. The most plausible mechanism of this rapidly induced unresponsiveness is that a subpopulation of antigen sensitive cells has been removed from the donor lymphocytes as they follow their physiological migration route through the spleen and lymphnodes.