We studied a highly reproducible spinal cord model of focal central nervous system ischemia produced by occlusion of the abdominal aorta in the rabbit just below the renal arteries. The neuropathology of the lesion at one week or longer is characterized by: 1. Necrosis of gray matter and relative sparing of white matter throughout the lumbar and sacral cord with periods of ischemia between 45 minutes and 2 hours; and 2. Selective necrosis of elements within the anterior horns of the gray matter (neurons) in the lumbar cord with periods of ischemia between 15 and 30 minutes and in the transition zone between normal and infarcted gray matter with periods of ischemia between 45 minutes and 2 hours. Within the time period that causes irreversible damage (15 minutes to 1 hour), the distribution, size, and severity of infarcts is proportional to the duration of ischemia. The degree of functional impairment correlated closely with the extent of tissue damage. Previous work on ischemia of the spinal cord in experimental animals is critically reviewed. The segmental topographic distribution of the lesion and its histologic characteristics are discussed in relation to two important pathophysiological mechanisms of injury in central nervous system ischemia: the microcirculatory network, which in turn governs the adequacy of collateral flow, and the differential susceptibility of cells in nervous tissue. Sequential regional spinal cord blood flow determinations will be necessary to establish the precise relationship between levels of blood flow over time and space and neuropathology.