The development of methods for the isolation of brain capillaries and brain capillary plasma membranes makes possible biochemical studies of the blood-brain barrier (BBB), which is made up of brain capillaries. Studies aimed at assessing the role of the BBB in the pathogenesis of specific neurologic diseases, e.g., Alzheimer's disease or multiple sclerosis, will necessitate the isolation of capillaries from brain involved with specific pathology. Such tissue is most readily available from banks containing frozen human brain. The present studies show that intact capillaries and capillary plasma membranes can be isolated from frozen human brain, including as little as five g of multiple sclerosis plaque tissue. Capillaries from frozen human brain are enriched in gamma-glutamyl transpeptidase, factor VIII antigen, and a 46K protein which has recently been shown to be a BBB-specific protein. These studies provide the basis for future biochemical studies of human brain microvessels in neurologic disease.