Distribution of viral antigens in the central nervous system of 25 cattle with a persistent bovine viral diarrhea virus (BVDV) infection was studied. Using a polyclonal antiserum produced in pigs and the direct immunofluorescence and immunoperoxidase technique, BVDV antigen was located exclusively in neurons. Predilection sites for viral persistence were cerebral cortex and hippocampus; in other areas of brain and spinal cord, viral antigens were in single neurons or small groups of neurons. There was no morphological evidence of cellular alteration due to viral persistence. Perivascular lymphocytic infiltrations were in affected nervous tissue. It is concluded that the central nervous system is an important location for persistence of BVDV.