F1 mice receiving sublethal whole-body x-irradiation (300 rads) or treatment with cyclophosphamide prior to the i.p. inoculation of parental spleen cells developed fatal graft-versus-host disease (GVHD). A greater survival rate was obtained when the inoculated parenteral spleen cells were obtained from BCGcw-preimmunized donors. The immunization of the F1 host with bacillus Calmette-Guerin cell walls (BCGcw) also increased host survival. The combined treatment of preimmunizing the host with BCGcw and of using spleen cells from BCGcw-immunized parental donors to initiate the GVHD resulted in producing the least severe GVHD and the greatest overall survival. The systemic transfer of x-irradiated spleen cells from BCGcw-immunized parental mice inhibited the fatal GVHD induced by the inoculation of normal parental spleen cells. These studies show that BCGcw immunization of the host or obtaining parental spleen cells from BCGcw-immunized animals resulted in improving the overall survival rate in graft-versus-host disease. BCGcw immunization induces suppressor cells and the decrease of graft-versus-host disease that was observed was most likely due to the induction of suppressor cells.