The central canal of the spinal cord is generally regarded as a vestigial structure that is obliterated after birth in 70% to 80% of the general population. This report describes the first detailed histological study of the human central canal in 232 subjects ranging in age from 6 weeks' gestation to 92 years. Whole spinal cords were harvested at autopsy and sectioned serially from the conus medullaris to the upper medulla. Histological findings and morphometric analysis of the cross-sectional luminal area were used to grade stenosis at seven levels of the canal. Varying grades of stenosis were present at one or more levels in none (0%) of 60 fetuses, one (3%) of 34 infants, three (18%) of 17 children, 21 (88%) of 24 adolescents and young adults, 67 (96%) of 70 middle-aged adults, and all 27 adults aged 65 years or older (100%). The stenotic process was most pronounced in the thoracic segments of the canal and involved more levels with higher grades of stenosis in older individuals. Histological findings consisted of disorganization of the ependymal epithelium, formation of ependymal rosettes or microcanals, proliferation of subependymal gliovascular buds, and intracanalicular gliosis. These features are consistent with a pathological lesion involving ependymal injury and scarring and are less compatible with an involutional or degenerative process. Stenosis of the central canal probably influences the anatomical features of syringomyelia and may account for variations in cavity formation such as the prevalence of holocord syrinxes in children, the formation of focal and paracentral syrinxes in adults, and the rare incidence of syrinx formation in many older individuals with acquired lesions known to produce syringomyelia.