Borna disease (BD) is a neurologic syndrome characterized by profound disturbances in behavior and the accumulation of specific antigens in limbic system neurons. The potency of brain homogenates from animals with BD to cause disease in normal animals is reduced by exposure to detergents. We have recently described isolation and characterization of clones derived from the BD agent. Here we present evidence that suggests that the BD agent is a negative-sense, single-strand RNA virus. The 8.5-kb genome of this virus appears to be associated with nuclei and encodes two major RNA transcripts of 2.1 and 0.8 kb.