Data were obtained which suggest that GBH reactions in vivo may reflect a complex of several separable components, any of which could independently produce a fatal reaction. Three congenic strains of mice were used as donors of cells to induce GvH reactions in anothr single strain of mice allogeneic to the donors. These donors were selected for their identity to each other at the minor histocompatibility loci (MiHL), with differences at the major histocompatibility complex (MHC or H-2), or in being T-lymphocyte deficient, characteristics thought to be involved in GvH reactions. Spleen cells from all three strains produced fatal GvH reactions. However, the resultant three survival curves differed significantly from each other. Infusion of spleen cells from normal C57Bl/10 donors (both H-2 and MiHL different from the SJL/J recipients) resulted in acute deaths amont the recipients, whereas infusion of spleen cells from athymic (nude) C57Bl/10 donors (both H-2 and MiHL different from the SJL/J recipients, and T-lymphocyte deficient) was followed by delayed deaths. Infusion of spleen cells from B10.S donors (H-2 compatible, MiHL incompatible with the SJL/J recipients) resulted in deaths which occurred during the interval intermediate between the acute and delayed deaths. To further explore the problem, the donor cells were exposed to monoclonal T-lymphocyte antibody plus complement before infusion. This treatment eliminated most of the deaths among the recipient of B10.S spleen cells, and prevented the acute deaths of the recipients of normal C57Bl/10 spleen cells, but had no effect on the survival of the recipients of spleen cells from athymic (nude) C57Bl/10 donors. Further, the major effect of T-lymphocyte antibody treatment of normal C57Bl/10 spleen cells was to shift the resultant survival pattern of the recipients to that of the delayed fatal GvH reaction seen in the recipients of cells from the athymic (nude) C57Bl/10 donors. Our interpretation of these data is that fatal GvH reactions in vivo may be composed of at least three independent and separable components: 1) MHC-determined and T-lymphocyte-mediated; 2) MiHL-determined and T-lymphocyte mediated; and 3) Primarily MHC, secondarily MiHL, determined with an unknown and possibly non-T-cell mediating factor.