The present study describes the pathologic changes and cellular apoptosis in the central nervous system (CNS) of fetal and neonatal small ruminants infected with border disease virus (BDV), as demonstrated by immunohistochemistry and in situ hybridization. Abortions of ewes and goats were observed, as were births of lambs and kids with poor survival rates and nervous signs. Lesions included cerebellar hypoplasia, porencephaly, hydranencephaly, and nonsuppurative meningoencephalomyelitis with hypomyelinogenesis. Viral antigens and RNA were present in neuropil, glial, and neuronal cells, especially in periventricular areas, cerebellum, and brainstem. TUNEL positivity and labeling of anti-bax and anti-caspases 3, 8, and 9 were detected in BDV-infected CNSs, especially in glial and neuronal cells. The double immunostaining and TUNEL assay revealed that in BDV-infected animals, not only were BDV-infected glial and neuronal cells undergoing apoptosis, but so were uninfected cells in close vicinity of BDV-infected cells. The expression of activated caspases 3, 8, 9; bax; and TUNEL in glial and neuronal cells of the infected fetal and neonatal kids were significantly (P < .05) higher than those of the infected fetal and neonatal lambs. Yet, the expression of bcl-2 in the CNSs of the infected fetal and neonatal lambs was higher (P < .05) in neuronal and glial cells than in those of the infected fetal and neonatal kids. The results suggest that cell death in the BDV-infected CNS is induced by intrinsic and extrinsic cascades of apoptotic pathways.