Mannosidosis, an inherited lysosomal storage disease, was diagnosed in two purebred Angus calves in the United States. Calf 1 was 5 months old and calf 2 was 7 months old when they were necropsied. Both calves had a history of progressive incoordination and ataxia. Gross postmortem findings included moderate hydrocephalus. Histologic examination revealed intracytoplasmic vacuolation of neurons throughout spinal cord and brain as well as in exocrine pancreatic cells, reticuloendothelial cells of the liver, and medullary sinusoids of lymph nodes. Biochemical study of 61 blood samples from the first calf's herd revealed bimodal distribution of enzyme activity for mannosidase. Two populations could be distinguished in that herd, those with normal mannosidase activity and those heterozygous for the disease.