The sera of 26 patients with graft versus host disease (GVHD) were analyzed for the presence of autoantibodies. Because the clinical spectrum of GVHD resembles some of the systemic collagen vascular diseases, particular attention was given to antinuclear antibodies and autoantibodies directed against saline soluble cellular antigens. 39% (10/26) of the patients had a positive ANA at a titer of greater than or equal to 1/80. Antibodies to double-stranded DNA were demonstrated in 4 sera (15%), to smooth muscle in 9 (41%) and to nucleoli in 6 (22%). Three sera had precipitating antibodies to saline extracts of rabbit thymus and/or bovine spleen. None of these precipitins showed lines of identity with known autoantibody systems. High titers of ANA were correlated with a previous diagnosis of acute lymphoblastic leukemia and multiple autoantibodies correlated with the severity of GVHD.