Beta-mannosidosis, an inherited defect of glycoprotein catabolism associated with deficiency of tissue beta-mannosidase and accumulation of Man(beta 1-4)GlcNAc and Man(beta 1-4)GlcNAc(beta 1-4)GlcNAc, appeared in four of 13 offspring of a single pair of clinically normal, related Nubian goats. Neurological examinations revealed that all four affected goats were unable to rise or walk. All had facial dysmorphism, dome-shaped skulls, small palpebral fissures, carpal contractures, hyperextension of the pastern joints, proximal muscle atrophy, intermittent ocular oscillations resembling pendular nystagmus, marked intention tremor, and deafness. With intensive care, three affected kids were hand-reared and then killed at 1, 7, and 21 days of age. Macroscopically, there were paucity of myelin in the cerebral and cerebellar hemispheres and ventricular dilatation. Microscopically, the extent and distribution of cytoplasmic vacuolation, myelin paucity, axonal spheroids, and filamentous expansions were evaluated in the cerebrum, cerebellum, brainstem, spinal cord, and peripheral nerves of the four affected kids and two age-matched, clinically normal kids. Widespread cytoplasmic vacuolation correlated with the previously reported accumulation of oligosaccharides in the brain and kidney and the deficiency of tissue beta-mannosidase. beta-Mannosidosis, not yet identified in man or other species, is characterized by distinctive neonatal clinical, pathological and biochemical features which differentiate it from the alpha-mannosidosis and other inherited diseases of glycoprotein catabolism.