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RESUMO.Este estudo teve o objetivo de determinar a frequência das enfermidades do sistema nervoso central que afetam bezerros até 12 meses de idade na região sul do Rio Grande do Sul. Foi realizado um estudo retrospectivo estabelecendo-se as principais enfermidades observadas nesta categoria de bovinos em um período de 36 anos. Foram revisados os protocolos de necropsia e de materiais remetidos ao Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas entre janeiro de 1978 e dezembro de 2015 referentes aos bovinos até 12 meses de idade que apresentavam sinais neurológicos. Foram resgatados os dados epidemiológicos referentes à procedência dos animais, tipo de criação, raça, idade e época de ocorrência e frequência de cada enfermidade. Foram identificados ABSTRACT.Santos B.L., Estima-Silva P., Coelho A.C.B., Oliveira P.A., Soares M.P., Sallis E.S.V., Bruhn F.R.P. & Schild A.L. 2018. [Central nervous system disease of calves in southern Brazil: a contribution to the differential diagnosis.] Doenças do sistema nervoso central de bezerros no sul do Rio Grande do Sul: uma contribuição ao diagnóstico diferencial. Pesquisa Veterinária Brasileira 38(4):685-691. Laboratório Regional de Diagnóstico, Faculdade de Veterinária, Universidade Federal de Pelotas, Campus Universitário, Pelotas, RS 96010-900, Brazil. E-mail: alschild@terra.com.br This paper aimed to determine the frequency of diseases of the central nervous system affecting calves under 12 months of age in southern Rio Grande do Sul. A retrospective study was conducted determining the main diseases observed in this category of cattle over a period of 36 years. We reviewed all the necropsy protocols and materials sent to the laboratory between 1978 and December 2015 relating to cattle under 12 months of age that showed neurological signs. The epidemiological data concerning the origin of the animals, raising system, breed, age and time of occurrence of each disease and frequency were taken from necropsy protocols. Out of 615 cases with neurological signs, 162 (26.3%) corresponded to cattle with age up to 12 months. The diagnoses were grouped by etiology of viral diseases (42.6%), bacterial diseases (19.1%), parasitic diseases (17.3%), congenital defects, hereditary diseases (6.2%), poisoning, mycotoxicoses (4.9%), nutritional deficiency and multifactorial diseases (2.5%), and trauma, degenerative diseases and neoplasms with 0.62% of diagnoses. Inconclusive cases represented 1.9% of the total diagnosed. In 1 to 90 day-old calves the main diseases observed were congenital defects, meningitis and encephalitis caused by bacteria. Central nervous system abscesses were also observed. In 4 to 9 month-old calves a lower frequency of disease were noted. Rabies was the most important disease diagnosed in this category. Babesiosis, rabies and encephalitis by bovine herpesvirus were the most important causes of death in 10 to 12 month-old calves.