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Degenerative lesions in the spinal cord white matter of 12 English Foxhounds and two Harriers between 3 and 6 years old were associated with a diet composed mainly of ruminant stomachs. Lesions were present throughout the length of the spinal cord and were more severe in ventral and lateral columns than in dorsal columns. Degenerate fibers were accompanied by astrocytic proliferation. Changes suggestive of a primary myelinopathy included vacuolated myelin sheaths around apparently intact axons and thick-thin transitions in myelin sheath thickness. Mixed sensory and motor peripheral nerves and muscle histochemical fiber type profiles appeared normal. Similarities were noted with the changes described in subacute combined degeneration of the spinal cord in human beings, a neuropathy caused by methionine and methylation deficiency in patients with vitamin B12 deficiency. Mean serum methionine levels were significantly lower (P greater than 0.01) and mean liver methionine synthetase levels were significantly greater (P greater than 0.01) in affected dogs restored to a balanced diet than in age-matched controls maintained on the balanced diet. The elevated methionine synthetase levels possibly reflected compensatory reactions to the associated dietary change.