Ingestion of the endocarp of the coyotillo fruit, Karwinskia humboldtiana, a shrub of the buckthorn family, causes "Buckthorn neuropathy" in man and animals. Two neurotoxic compounds T496 and T544 were isolated from the endocarp and each toxin was dissolved in sesame oil and injected into the sciatic nerve of rats. The nerves were subsequently examined by teasing and as sections by light and electron microscopy. During the first 3--4 days after injection, oil droplets, probably containing toxin, were observed in the cytoplasm of Schwann cells with intact myelin sheaths. Clinical signs of weakness in the limb first appeared at 5--6 days and were accompanied by segmental demyelination mainly of the larger fibres. These observations suggest that the toxins have a primary action on Schwann cell metabolism. The results of local injection of purified toxins are discussed in relation to reports of nerve damage in animals following oral administration of the endocarp where intramyelin vacuole formation and segmental demyelination are prominent features.