A clinical and neuropathological study of a case of xeroderma pigmentosum with severe neurological abnormalities was performed. The patient developed sensitivity to the sun, followed by freckles and malignant skin tumors. Some years after the onset of the cutaneous symptoms, a slowly progressive mental deterioration was noted. Subsequently, dysarthria, increased sensitivity and a tendency to cry and to be easily frightened developed together with ataxia and spasticity of the limbs. Late in the course of the disease the patient was severely disabled because of spastic tetraplegia. The clinical examination revealed generalized slowing in EEG, mixed sensory and motor neuropathy in EMG, thick skull, both cerebral cortical atrophy and ventricular dilatation in computed tomography and marked decrease in cerebrospinal homovanillic acid content. The neuropathological study showed marked loss of neurons in the basal nucleus of Meynert, the substantia nigra, the cerebellum, medulla and spinal cord. Diffuse loss of neurons was noted in the cerebral cortex and in the deep cerebral nuclei. In the nerve cells, a high amount of cytoplasmic lipofuscin was observed in some areas of CNS. The sciatic nerve showed marked loss of axons and heavy deposition of collagen around the remaining nerve fibers. The present neuropathological findings explain many of the clinical symptoms observed in xeroderma pigmentosum and show similarities with those observed in olivopontocerebellar atrophy, although the basic mechanism for the CNS damage is still unclear.