Despite advances in immunosuppression over the past ten years, the overall longevity of the cardiac allograft has only minimally increased. The average allograft half-life has increased only 6 months (8.8 years to 9.4 years) between the time periods of 1986–1990 and 1991–1997. 1 Hosenpud J.D. Bennett L.E. Keck B.M. Fiol B. Boucek M.M. Novick R.J. The Registry of the International Society for Heart and Lung Transplantation Fifteen Official Report—1998. J Heart Lung Transplant. 1998; 17: 656-668 PubMed Google Scholar The single major cause of allograft loss after one year remains allograft coronary artery disease (ACAD). 1 Hosenpud J.D. Bennett L.E. Keck B.M. Fiol B. Boucek M.M. Novick R.J. The Registry of the International Society for Heart and Lung Transplantation Fifteen Official Report—1998. J Heart Lung Transplant. 1998; 17: 656-668 PubMed Google Scholar This entire issue of the Journal of Heart and Lung Transplantation is devoted to the potential etiologic factors as well as the clinical manifestations of ACAD. Traditionally, the immune response to allotransplantation has been divided into the cellular (T-cell) and humoral (B-cell) processes. While it is likely that both processes are activated and ongoing simultaneously in most allograft recipients, patients who appear to have a predominately humoral process have been reported to have worse long-term outcomes. 2 Hardy M. Suciu-Foca N. McKiernan T. et al. The development of specificity of anti-B cell antibodies during humoral rejection of kidney allografts. Transplant Proc. 1979; 11: 389-392 PubMed Google Scholar , 3 Mohanakumar T. Waldrop J.C. Phipps M. Mendez-Picon G. Kaplan A.M. Lee H.M. Serologic characterization of antibodies eluted from chronically rejected human renal allografts. Transplantation. 1981; 32: 61-66 Crossref PubMed Scopus (63) Google Scholar , 4 Hess ML, Hastillo A, Mohanakumar T, Cowley MJ, Vetrovec G, Szentpetery S, Wolfgang TC, Lower RR. Accelerated atherosclerosis in cardiac transplantation: role of cytotoxic B-cell antibodies and hyperlipidemia. Circulation 1983;68(suppl II):II-94–101. Google Scholar , 5 Rose E.A. Smith C.R. Petrossian G.A. Barr M.L. Reemtsma K. Humoral immune responses after cardiac transplantation correlation with fatal rejection and graft atherosclerosis. Surgery. 1989; 106: 203-208 PubMed Google Scholar , 6 Rose E.A. Pepino P. Barr M.L. Smith C.R. Ratner A.J. Ho E. Berger C. Relation of HLA antibodies and graft atherosclerosis in human cardiac allograft recipients. J Heart Lung Transplant. 1992; 11: S120-S123 PubMed Google Scholar , 7 Reed E.F. Hong B. Ho E. Harris P.E. Weinberger J. Suciu-Foca N. Monitoring of soluble HLA alloantigens and anti-HLA antibodies identifies heart allograft recipients at risk of transplant-associated coronary artery disease. Transplantation. 1996; 61: 566-572 Crossref PubMed Scopus (130) Google Scholar , 8 Suciu-Foca N. Reed E. Marboe C. Harris P. Xi Y.P. Yu-Kai S. Ho E. Rose E. Reemtsma K. King D.W. The role of anti-HLA antibodies in heart transplantation. Transplantation. 1995; 51: 716-724 Crossref Scopus (177) Google Scholar , 9 Hammond E.H. Yowell R.L. Nunoda S. et al. Vascular (humoral) rejection in heart transplantation pathologic observations and clinical implications. J Heart Transplant. 1989; 8: 430-443 PubMed Google Scholar , 10 Hammond E.H. Yowell R.L. Price G.D. et al. Vascular rejections and its relationship to allograft coronary artery disease. J Heart Lung Transplant. 1992; 11: S111-S119 PubMed Google Scholar Patients developing circulating anti-HLA antibodies or the immunohistopathologic pattern of vascular rejection early after cardiac transplantation have demonstrated poorer survival and increased risk for the development of ACAD. 4 Hess ML, Hastillo A, Mohanakumar T, Cowley MJ, Vetrovec G, Szentpetery S, Wolfgang TC, Lower RR. Accelerated atherosclerosis in cardiac transplantation: role of cytotoxic B-cell antibodies and hyperlipidemia. Circulation 1983;68(suppl II):II-94–101. Google Scholar , 5 Rose E.A. Smith C.R. Petrossian G.A. Barr M.L. Reemtsma K. Humoral immune responses after cardiac transplantation correlation with fatal rejection and graft atherosclerosis. Surgery. 1989; 106: 203-208 PubMed Google Scholar , 6 Rose E.A. Pepino P. Barr M.L. Smith C.R. Ratner A.J. Ho E. Berger C. Relation of HLA antibodies and graft atherosclerosis in human cardiac allograft recipients. J Heart Lung Transplant. 1992; 11: S120-S123 PubMed Google Scholar , 7 Reed E.F. Hong B. Ho E. Harris P.E. Weinberger J. Suciu-Foca N. Monitoring of soluble HLA alloantigens and anti-HLA antibodies identifies heart allograft recipients at risk of transplant-associated coronary artery disease. Transplantation. 1996; 61: 566-572 Crossref PubMed Scopus (130) Google Scholar , 8 Suciu-Foca N. Reed E. Marboe C. Harris P. Xi Y.P. Yu-Kai S. Ho E. Rose E. Reemtsma K. King D.W. The role of anti-HLA antibodies in heart transplantation. Transplantation. 1995; 51: 716-724 Crossref Scopus (177) Google Scholar , 9 Hammond E.H. Yowell R.L. Nunoda S. et al. Vascular (humoral) rejection in heart transplantation pathologic observations and clinical implications. J Heart Transplant. 1989; 8: 430-443 PubMed Google Scholar , 10 Hammond E.H. Yowell R.L. Price G.D. et al. Vascular rejections and its relationship to allograft coronary artery disease. J Heart Lung Transplant. 1992; 11: S111-S119 PubMed Google Scholar