SUMMARYAdult, nonirradiated C57BL/6J {H-2bfemale mice do not show splenic enlargement following the injection of allogeneic (H-2k) spleen cells. Adrenalectomized, noninjected controls show splenic enlargement at 7, 14, and 21 days after surgery. When adrenalectomized mice are injected with allogeneic spleen cells, the spleens do not enlarge by the 7th day but, by the 14th day, splenic enlargement exceeds that seen in noninjected, adrenalectomized controls. By the 21st day, the spleens, although still enlarged, do not exceed in weight those of the noninjected adrenalectomized controls. Both of these effects —splenic enlargement following adrenalectomy and modification of this enlargement by injection of allogeneic cells—are abolished by injection of cortisone acetate. It is suggested that adrenalectomy may modify the host-versus-graft reaction of mice.