Lesion distribution in the spinal cord was investigated by sampling an average of 26 spinal cord segments in each of ten dogs severely affected by canine globoid leukodystrophy (GLD). GLD lesions were quantified by subdividing spinal white matter into small unit areas and judging the quartile extent of lesion involvement for each unit area. Along the length of the spinal cord, lesions declined from cranial to caudal, decreasing precipitously in the midlumbar region. The lumbosacral region had the least amount of lesion, and, based on lesion per unit area, the thoracic region was most severely involved. The dorsal funiculus had the greatest concentration and the least dispersion of lesion generally amoung the three funiculi. White matter at the periphery of the spinal cord was involved earlier and more severely than white matter adjacent to gray matter. Amount of lesion per spinal cord could be estimated adequately by sampling one segment from each of five regions. Dogs could be divided into two groups based on rate of lesion development. Clinical signs did not correlate closely with total amount of lesion per spinal cord. Of the total amount of variability among dogs in amount of spinal pathologic involvement, 78% could be accounted for by a mathematical model expressing spinal cord pathologic involvement as a quadratic function of age at onset and duration of the clinical syndrome.