We review the pathogenesis, epidemiology and patient cases of transfusion-associated graft-versus-host disease (TA-GVHD) in the context of host inability to eliminate viable donor T-lymphocytes. This review is based on the published English-language literature pertaining to TA-GVHD, including case reports with HLA data on transfusion recipients as well as blood donors. The role of shared histocompatibility antigens between the donor and the recipient in promoting TA-GVHD is discussed critically. Since TA-GVHD is usually a fatal disease for which effective therapy is lacking, prevention is of utmost importance and guidelines for gamma-irradiation of cellular blood products are presented. TA-GVHD has been described in immunodeficient as well as in immunocompetent hosts, and following blood product transfusions from related as well as from unrelated donors. This review includes analysis of patient data in each of these settings and probability estimates based on principles of population genetics. We emphasize that transfusion of blood products from individuals who are homozygous at the HLA loci to heterozygous recipients who share that HLA haplotype occurs at a frequency proportional to the genetic homogeneity of the population and that the process mediating TA-GVHD in such instances appears to be independent of the host's immune status.