The symptomatology and outcome of three of our own cases with Melphalan overdose are presented. The literature regarding Melphalan overdose and its toxicity when given in normal and high doses is reviewed. Two of our cases with injection of less than 100 mg/m2 recovered from marrow aplasia within 3 weeks without major complications. The third patient died 6 days after injection of 290 mg/m2 Melphalan, probably due to cardiac arrhythmia before complete marrow failure had established. After intravenous application of more than 125 mg/m2 gastrointestinal side effects such as hemorrhagic diarrhea or even bowl perforation may be observed. These, together with a syndrome of inadequate ADH-secretion and electrolyte disturbances were the predominant clinical problems and the reasons for early death before infectious or bleeding complications due to prolonged marrow aplasia occur. Therapeutic measures are discussed. Due to the lack of a clinically useful antidote and detoxification method only symptomatic treatment is recommended. Colony stimulating factors such as GM-CSF G-CSF may improve the prognosis of moderate to severe Melphalan overdose.