The present review summarizes some of this laboratory's recent findings and interpretations concerning the cellular interaction involved in graft-versus-host-induced immune deficiency. Our results indicate that GvHID induced by parental T cell recognition of allogeneic F1 class I plus class II MHC determinants abrogates CTL responses involving both self + X and H-2 alloantigen recognition. In contrast, GvHID induced by parental T cell recognition of only allogeneic F1 class II antigens reduces self + X CTL responses, but does not reduce allogeneic CTL activity. Parental T cell recognition of only class I H-2 antigens does not affect CTL responses. The GvHID is associated with a loss of ability of spleen cells from GvH mice to produce IL 2 and to express IL 2 receptors after stimulation with T cell mitogens. This reduction in IL 2 potential is associated with a reduction in T cells that survive mitogenic stimulation in culture. Freshly explanted spleen cells from GvHID mice exhibit normal numbers of T cells. Our findings are discussed in terms of there being distinct helper T cell pathways for the generation of CTL to self + X and alloantigens (Singer et al. 1984). The model proposed for selective loss of self + X T cell immunity in class II-induced GvHID is discussed with respect to the parallel selective loss of self + X CTL activity in the developmental stages of acquired immune deficiency syndrome (AIDS).