In order to identify possible morphological changes which occur in the anterior horn of normal individuals during aging, 40 controls with no neurological disease were studied. Brain and spinal cord tissue was processed according to a brain banking protocol. Controls were grouped according to age in 10 year intervals. Serial sections (20 microm) of formalin fixed, paraffin-embedded tissue were obtained, from each cervical, thoracic and lumbar spinal cord segment. Every 5th section (until 2 mm) was stained with haematoxylin and eosin and the numbers of motor neurons in the anterior horn counted at x400 magnification. Descriptive statistical analysis was performed using the SPSS program. Parallel sections (5 microm) of the same spinal segments were immunostained with a panel of antibodies including glial fibrillary acidic protein (GFAP), tau, ubiquitin and two phosphorylated neurofilaments subunits. Significant neuronal loss with aging was found by regression line analysis where three equations were used to calculate the number of motor neurons by age in each spinal segment. In 24/40 cases spheroids were observed and they were more numerous in the lumbar segment. GFAP staining revealed a distinctive cellular pattern in the anterior horn of oldest cases. Large and intensely stained astrocytes were seen in the anterior horn of cases aged over 75 years. The number of astrocytes increased progressively with age up to 70 years. Some of the changes observed in the present study may be the result of a selective vulnerability of large motor neurons to aging which could play an important role in the progression of MND. Most of these changes may also have similar pathophysiological mechanisms.