The purpose of this study was to evaluate by light microscopy the effects of ionizing radiation on spinal cords of rats irradiated when three days of age and killed at intervals up to 28 months after irradiation. The amounts of x-rays administered (2,000 R; 1,000 R; 500 R ) were those which had been demonstrated by short-term studies in this laboratory to cause either no histopathologic changes or only transient, reparable alterations. The most significant and previously unreported finding was the development, usually restricted to the gray matter, of elongated, spindle-shaped cells that produce prodigious amounts of fibers clearly demonstrated by the Wilder's reticular stain. In cases where extensive cellular development had occurred, these cells were oriented around the perikarya of the large ventral motor neurons and formed a well-developed capsule of reticular fibers. This phenomenon occurred more frequently in rats receiving the greater amounts of radiation and killed 12 months or more after exposure. The other observation of interest was the development of lesser amounts of connective tissue-producing cells in the dorsal gray matter, where these cells were seen initially in the substantia gelatinosa. The significance of these changes is discussed in relation to previously reported long-term effects of ionizing radiation on the central nervous system. Short-term studies, having observation periods of 70 days or less, have shown that the architecture of the immature or early postnatal spinal cord in the rat can be altered by ionizing radiation. These alterations, always involving neuroglia and myelin, are related to the amount of radiation administered (Gilmore, '63b; Rodgers, '65; Gilmore, '65; Gilmore, '66). For example, 4,000 R localized to the lumbosacral spinal cord results in a rapid loss of most neuroglia from the irradiated area and a consequent state of hypo-or amyelination (Gilrnore, '63b; Rodgers, '65; Gilmore and Arrington, '67). In many of these cases, vascular disruption and necrosis of a variable extent then ensue (Gilmore and Arrington, '67). The intact, irradiated areas of these animals, however, show development of intramedullary Schwann cells and myelin of the peripheral type in the dorsal funiculi, dorsal gray, and sometimes in the ventral areas (Gilmore and Duncan, '68). Administration of 2,000 R also induces a rapid loss of many neuroglia accompanied by retardation in myelination (Rodgers, '65; Gilmore, '66). By three weeks following irradiation, the neuroglial population is being reconstituted, and delayed myelinogenesis occurs; by one month post-irradiation the spinal cords appear to be normal (Gilmore, '66). No necrosis occurs at this dose level and further studies showed that the vascular changes are transient (Gilmore, '69). When 1,000 R or 500 R is administered, no morphological changes occur within two months after irradiation (Rodgers, '65).These data indicate that the presence or absence of changes and the pattern of changes is dependent upon the amount of radiation adm...