Young seronegative ferrets were intracerebrally inoculated with a neurotropic strain of canine parainfluenza (CPI) virus and serially killed at intervals after infection for subsequent viral immuno-peroxidase, light microscopical and scanning electron microscopical evaluation. The CPI virus infection resulted in a self-limiting non-suppurative ependymitis and choroiditis with associated ependymal cell degeneration. These changes were accompanied by paraventricular and perivascular cellular infiltrates of lymphocytes and monocytes, predominantly in the fourth ventricle and the cervical sipinal cord and less frequently in the lateral ventricles and Sylvian duct. The inflammatory lesions were first detected on post-inoculation day (PID) 8 and had largely resolved after PID 22. Two animals showed multifocal axonal degeneration in the mesencephalon and vestibular nucleus, respectively. Immuno-histocytochemistry showed that virus replication was restricted to ependymal and subependymal cells and was most prominent on PID 4. No prominent residual lesions were present in convalescent animals. Virus-neutralizing CPI antibodies developed by PID 9 and increased slowly thereafter.