We have previously reported a pathological investigation of peripheral neuropathy in a horse with knuckling. This report describes details of the muscle and peripheral nerve lesions in two additional cases of light horse yearlings with knuckling. The skeletal muscles showed neurogenic atrophy characterized by scattered single angular fibers, fiber grouping, and fiber-type grouping. The severity of muscle lesions increased distally; that is, both fore- and hindleg muscles were affected more severely than cervical and dorsal muscles. In the peripheral nervous system, a number of Renaut bodies appeared to be common in the nerve fascicles. Pathological alterations indicating demyelination, remyelination and regeneration of nerve fibers were occasionally observed. The most common abnormality was myelin ovoids or myelin debris infiltrated by macrophages. Occasionally, myelinated axons were seen containing accumulations of organelles, often associated with buckling of the myelin. The myelin sheath occasionally formed axonal outpouching containing accumulations of mitochondria and dense lamellar bodies. Histochemically, intramuscular nerve fibers presented multiple arborization and collateral ramification, indicating relapsing denervation and reinnervation. Also seen were the fibers with myelin balloons or swollen segments considered as being degenerative processes. The distribution patterns of muscular lesions in the affected animals were indicative of systemic distal denervation atrophy. In addition, peripheral nervous lesions that selectively involve the distal parts of axons and an absence of abnormalities in neuronal cell bodies in the spinal cord suggest a dying-back neuropathy. It was concluded that this disease should be classified as a distal axonopathy.