Chronic idiopathic thrombocytopenic purpura (ITP) is most often treated successfully with steroids and/or splenectomy. In those who fail to respond with the foregoing treatment, immunosuppressive drugs are sometimes added to the regimen. Cyclophosphamide has been reported heretofore to be effective with a minimum of side effects and complications. However, the use of alkylating agents and the induction of a second malignancy is now well recognized. This report describes three cases of refractory ITP treated with cyclophosphamide who subsequently developed an acute non-lymphocytic leukemia. Cyclophosphamide should be used with discretion in the treatment of chronic idiopathic thrombocytopenic purpura which is a non-neoplastic disorder.