A 27-year-old man, immunosuppressed from recent chemotherapy for metastatic Ewing's sarcoma, presented with a 1-week history of a painful, pruritic, papulovesicular eruption on the hands and feet. A diagnosis of hand, foot and mouth disease was made based on histology, detection of Enterovirus ribonucleic acid by polymerase chain reaction on a swab from a vesicle, and a four-fold increase in Enterovirus antibody levels. At no stage however, were there lesions in the mouth. Another unusual feature in this case was a prolonged course, presumably as a result of immunosuppression. After 3 1/2 weeks he was commenced on oral aciclovir 200 mg five times daily, with subsequent resolution of all lesions within 5 days. There may be a role for systemic aciclovir in some patients with hand, foot and mouth disease.