Transfusion-associated graft-vs.-host disease (tGVHD) is a severe disease usually affecting immunocompromised hosts with haematological neoplasia. Two patients with acute leukaemia are reported, who developed fatal tGVHD after blood transfusions. Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial leucocyte adhesion molecule 1 (ELAM-1) expression and the CD4/CD8 ratio were assessed in lesional skin. ICAM-1 was strongly expressed on epidermal keratinocytes and endothelial cells (EC) and correlated with HLA-DR staining. VCAM-1 was strongly expressed on EC in the superficial dermal vessels. ELAM-1 stained weakly on EC in some of the superficial vessels. CD8+ lymphocytes showed prominent epidermotropism; the CD4/CD8 ratio was 0.8 in case 1 and 1.2 in case 2. Infiltrating cells were positive for CD3, CD11a, and CD18. Langerhans' cells were almost completely absent. The dermatologist must be aware of the importance of such a rare, unexpected and almost always fatal complication of blood transfusion, in order to make an early diagnosis. Irradiation of blood products is the only effective way to prevent tGVHD in all subjects at risk.