Histopathological changes in kidneys subjected to 45 min of isothermic unilateral ischaemia in the acute phase and 1 week and 1 month after primary damage were studied at the electron microscopic level. During the first week after recirculation long homogeneous cylinders, probably consisting of Tamm-Horsfall protein, developed in the medullary parts of the nephron, and after 1 month of recirculation there were two types of nephrons: (1) nephrons with a normal histological appearance and (2) degenerated nephrons. The latter group gave rise to crypts in the outer cortical area. It is hypothesized that the generation of the long Tamm-Horsfall cylinders in the thick ascending limb of the loop of Henle plays an important role in the long-term outcome of the kidney after the primary damage. The persistent blockade caused by these cylinders will lead to precipitation of the ultrafiltrate, resulting in long cell-protein cylinders in the proximal parts of the nephron. This precipitation will proceed in the retrograde direction, reaching the mother glomeruli, eventually leading to total degeneration of the nephron.