A heritable bone marrow disorder, pathophysiologically identical to human hereditary spherocytosis was selected as a model system for investigation of the treatment of inherited marrow disease by hemopoietic homografts in the newborn period. Bone marrow suspensions were prepared from femur and tibia of adult normal donor and injected intravenously into the facial vein or retroorbital plexus of newborn spherocytic animals within 24 hr after birth. Successful replacement of pathologic by normal marrow was demonstrable in most recipients. Reticulocyte levels and osmotic fragility remained essentially constant for 1 yr following initial bone marrow transplants, indicating apparent stability of successful grafts. Skin grafts from the oniginal bone marrow donors to the respective recipients were done between 3 to 6 months of age. Skin grafts between control animals were rejected in 2 weeks, indicating that histocompatibility genes differed between various individuals, but spherocytic individuals successfully transplanted with normal marrow maintained skin grafts up to 1 yr. The data show that immunologic tolerance conferred by marrow injections into the newborn extends to tissues other thin the marrow. Several treated mice, not showing evidence of red cell changes, exhibited variable prolongation of skin graft survival, indicating that even in the absence of significant erythropoietic transplants some donor cells had been successfully transferred at birth and had induced partlal tolerance. The mechanism by which the normal donor marrow replaces spherocytic erythropoiesis in the newborn is not known but could relate to seeding of relatively empty marrow cavities by the injected cells preventing the animal's own marrow cells from functional development. (TCO)