Lethally irradiated (850 rads) DBA/2 mice which had been transplanted 10 months previously with 2 times 10-6 bone marrow cells from 3-week-old donors of the H-2-histocompatible NZB, BALB/c and DBA/2 strains were examined for manifestations of autoimmune disease. Also studied were lethally irradiated (950 rads) NZB mice grafted with NZB marrow. Strongly positive antinuclear antibody responses were present in all NZB and DBA/2 recipients of NZB marrow, but absent in DBA/2 mice grafted with BALB/c and DBA/2 marrow cells. The antinuclear antibody-positive animals had glomerulonephritis with the deposition of globulin in or along the basement membranes. These observations support the view that the potential for autoantibody formation and subsequent autoimmune disease development is inherent to the NZB hemopoietic stem cell and their progeny.