Individuals with spinal cord injury (SCI) currently have a longer life span as a result of recent improvements in medical care. As in the able-bodied population, cardiovascular disease is the leading cause of death in persons with SCI, but it appears to occur at younger ages in those with SCI than in the able-bodied population. The reduction in level of activity and adverse changes in body composition caused by SCI have profound metabolic consequences that may influence the progression and severity of coronary artery disease. Metabolic sequelae of SCI include disorders of carbohydrate and lipid metabolism. Almost half of the 45 active, healthy subjects with paraplegia we studied have a disorder of carbohydrate tolerance, 1 in 5 subjects having a diabetic oral glucose tolerance test. Hyperinsulinemia is found in those with abnormal glucose tolerance. Subjects with paraplegia having impaired glucose tolerance or diabetes mellitus are significantly older than those with normal glucose tolerance. High-density lipoprotein cholesterol is markedly depressed, and low density lipoprotein is relatively elevated. Radionuclide myocardial perfusion imaging after upper body ergometry exercise reveals latent coronary artery disease in 12 of 19 subjects with paraplegia.