When a patient receives blood from a closely related donor, there is the potential for transfusion-associated graft-versus-host disease (TA-GVHD). With a mathematical model, the potential risk of TA-GVHD was derived for six classes of related donors. This risk was considered to be present when an HLA-heterozygous patient received blood from a donor who was homozygous for one of the patient's haplotypes. Calculations showed that second-degree related donors present a greater risk of TA-GVHD than some (siblings) but not all (parents, children) first-degree related donors. Moreover, there is, in general, no sharp cutoff of risk among the various classes of donors. These results should be considered in the determination of a policy for the irradiation of directed-donor units.