To investigate the effects of a permanent interstitial source of gamma-irradiation on normal brain tissue, single iridium-192 (Ir-192) wires (1.05 mCi) were stereotactically implanted into the left centrum semiovale of adult dogs (survival times, 25, 46, 74, 230 and 362 days). Within 25 days, a coagulation necrosis developed in the immediate vicinity of the radioactive source. In later stages, the necrosis increased in size and became progressively mineralized. Staining for extravascular immunoreactive serum proteins revealed the presence of a chronic perifocal vasogenic edema, which extended into the white matter of the entire ipsilateral hemisphere. This edema persisted through all stages and showed a significant decrease only in the animal with a 1-year survival. A reactive gliosis with formation of a dense network of glial fibrillary acidic protein-positive astrocytes developed around the central necrosis in the adjacent white matter and, at later stages, in the contralateral hemisphere. Demyelination was restricted to the ipsilateral centrum semiovale without affecting the internal capsule or the contralateral hemisphere. It was present as early as 25 days and showed no tendency to increase at later stages. Analysis of the sequential morphological changes following Ir-192 implantation suggests that the central coagulation necrosis represents a direct radiation effect, the sharp focal delineation of which can be explained by the physical characteristics of the radiation source, i.e., rapid fall-off of the dose at short distances. Due to the continuous emission of radiation energy, there is a perifocal zone with overlapping of progressive radiation damage and tissue organization. This focus becomes the source of a chronic vasogenic edema, which in turn is most likely to be responsible for the partial demyelination of the adjacent centrum semiovale. The widespread reactive gliosis observed at all stages may also, in part, be a consequence of chronic vasogenic edema, but its distribution suggests that direct radiation effects may also be involved.