In a study of 27 patients receiving marrow grafts from HLA-identical donors, the immune response capacity of donor T cells measured pretransplant was compared with the incidence and severity of post-transplant acute graft-versus-host disease (GVHD). Donors were categorized as either high responders or low responders based on their responsiveness to monocyte-dependent soluble antigens and to alloantigens expressed on a B-lymphoblastoid cell line. The high or low responder status of donor cells as defined by response to soluble antigen did not correlate with the incidence of acute GVHD in patients receiving transplants from these donors. The responder status of donor cells as defined by response to alloantigen, however, did correlate with incidence of post-transplant GVHD. Of nine patients receiving marrow from low responder donors, only two developed GVHD (Grades I-II). Conversely, of 18 patients receiving marrow from high responder donors, 13 developed GVHD (Grade I-IV) (chi 2 = 3.71; d.f. = 1, p = 0.05), with nine of the 13 developing moderate to severe Grade II-IV GVHD (chi 2 = 2.60; d.f. = 1, p = 0.10). These results indicate that pretransplant testing of donor T cells for response to alloantigen may identify those patients who will be at increased risk of developing clinically significant acute GVHD following marrow transplantation. Since there was only a trend toward statistical significance, however, these data require confirmation in a prospective study with larger number of patients.