Von Recklinghausen's neurofibromatosis is a dominantly inherited cancer syndrome. Its gene encodes neurofibromin, a protein with ras GTPase-activating function (rasGAP) and, therefore, all NF1-associated pathology is thought to originate from selective deregulation of the ras pathway. We have constructed a variety of mouse models for NF1 that permit recapitulation of the most common tumors seen in patients. In addition, these mouse models offer insights into tumor origin and into paracrine interactions. Given the molecular and pathological fidelity of the mouse tumors to the human counterparts, it is hoped that these mouse strains will serve as effective tools for therapeutic discovery.