JC virus is a human papovavirus implicated as the causative agent in the demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV has also been associated with tumors in some PML patients. It is the intent of this study to determine if introduction of JCV into transgenic mice would provide an animal model to study these human diseases. Two distinct disease patterns were observed. Three lines of mice developed a neurological disorder, in which myelin production was diminished or absent in the central nervous system. This provides a model to study the demyelinating disease PML. Four transgenic mice developed tumors, diagnosed as neuroblastomas of the adrenal medulla. Production of these mice may provide an insight into and how tumors are induced by the JC virus and how analogous tumors arise in humans.