Autopsies from nine patients who had received a cardiac allograft transplant and one with a combined heart-lung transplant were assessed for histologic evidence of pseudo-graft-versus-host disease (pseudo-GVHD). Five of the ten patients had GVHD-like changes in two or more tissues, including prominent lymphocyte-associated bile duct injury consistent with marked hepatic pseudo-GVHD and mild cutaneous changes resembling GVHD. A sixth recipient had marked changes in the liver, but autopsy restrictions prevented examination of the skin. A seventh recipient had only mild pseudo-GVHD changes limited to the skin. In contrast, a series of six patients who were candidates for cardiac transplant had no specific pathologic changes suggesting pseudo-GVHD. The majority of those with pseudo-GVHD had received nonirradiated blood product transfusions, raising the possibility of posttransfusion engraftment and GVHD. Unlike the posttransfusion GVHD, however, two of the six developed GVHD-related complications late with a latent period of five and 9.5 months, and two recipients received no transfusions. All were receiving only modest doses of immunosuppressive agents at the time they developed liver function abnormalities, including low or tapering doses of cyclosporine (CsA). In some of these recipients, therefore, the pseudo-GVHD changes may well represent an autoimmune reaction resembling the post-CsA model of autoimmune disease.