Dermatologic side effects of cytosine arabinoside (ara-C) are rare and most commonly occur after high-dose (more than 100 to 200 mg/m2 per day) therapy has been administered for several days. Although vascular reactions after combination chemotherapeutic regimens with ara-C have been anecdotally described, they have not been previously reported after single-agent chemotherapy with ara-C. Herein we describe two patients with acute nonlymphoblastic leukemia in whom cutaneous small vessel necrotizing vasculitis developed after high-dose single-agent chemotherapy with ara-C. Cutaneous lesions developed 3 to 5 days after initiation of therapy and resolved spontaneously within a week after the chemotherapeutic regimen was completed. No evidence of systemic vasculitis was present in either patient. Prior experimental data have demonstrated a direct toxic effect of ara-C on endothelial cells, and this outcome may represent the underlying mechanism of vascular injury.