Chronic graft-versus-host disease (GVHD) is a common long-term complication of allogeneic hematopoietic stem-cell transplantation (HSCT), and is responsible for morbidity, mortality and a decrease in quality of life of patients after SCT. Polymyositis, which usually co-occurs with other manifestations of GVHD, has previously been reported. However, polymyositis as the sole manifestation of chronic GVHD following donor lymphocyte infusion (DLI) is rare. We report a 30-year-old man with Hodgkin's lymphoma who developed acute polymyositis following treatment by DLI 4 months post-allogeneic HSCT. The patient developed fever and generalized myalgia 22 days after a single dose of DLI. Laboratory testing showed elevated muscle enzymes and myopathic abnormalities on electromyographic examination. Muscle biopsy showed features of acute polymyositis, with widespread foci of muscle fiber necrosis associated with infiltration of small mononuclear cells. Twenty-four hours after diagnosis, the patient developed a fatal ventricular arrhythmia. Cardiac involvement may occur in association with polymyositis, but usually occurs in elderly patients after several months of illness. The present case highlights the importance of systematic cardiac evaluation when a diagnosis of polymyositis is initially made to exclude this infrequent presentation of chronic GVHD characteristically associated with some HLA-DR haplotypes.