Acute graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation but is only rarely observed after solid organ transplantation. We describe a 68-year-old man who developed a maculopapular eruption 7 days following orthotopic liver transplantation for cirrhosis with malignant transformation due to haemochromatosis. At day 20, the patient complained of nausea, vomiting, diarrhoea and fever. Skin biopsy revealed a lymphocytic infiltrate at the dermoepidermal interface, vacuolization of basal cells and epidermal dyskeratosis. Immunohistochemistry showed HLA-DR and intercellular adhesion molecule-1 expression of lesional keratinocytes. HLA-typing of peripheral blood lymphocytes demonstrated circulating lymphocytes of donor origin. Endoscopy revealed extensive erosions of the oesophagus, stomach and duodenum that on histology disclosed multifocal loss of crypts, lymphocytic infiltrates and epithelial cell death. A diagnosis of acute GVHD was made, and high-dose immunosuppressive therapy with azathioprine and methylprednisolone was instituted. The skin and gastrointestinal symptoms subsided within 4 weeks, but the patient died from severe infectious complications 105 days after transplantation. We conclude that acute GVHD is a rare but potentially fatal complication of liver transplantation. Skin lesions are an early sign of acute GVHD and thus represent an important tool for early diagnosis.