We generated retinoid-deficient adult rats by the removal of retinoids from their diet. We show that their motoneurons undergo neurodegeneration and that there is an accumulation of neurofilaments and an increase in astrocytosis, which is associated with motoneuron disease. These effects are mediated through the retinoic acid receptor alpha. The same receptor deficit is found in motoneurons from patients suffering from spontaneous amyotrophic lateral sclerosis. Furthermore, we show that there is a loss of expression of the retinaldehyde dehydrogenase enzyme II in motoneurons. Therefore, we propose that a defect in the retinoid signalling pathway is in part be responsible for some types of motoneuron disease.