The response to injury of the cerebrum of the neonatal rat was studied in knife wounds by using both light and electron microscopical, and immunohistochemical, techniques. The rats were injured at 2, 4, 8, 12, 16 and 20 days
post natum
and the tissues examined 8 days later. A mature scar, that is, a layer of fibrous tissue separated from the injured neuropile by a glia limitans, is not formed in the brains of rats lesioned before 8 days
post natum
. Before this time, the neuropile of the severed hemisphere grows together and both the glia limitans externa and ventricular lining are repaired. The only evidence of the wound, 20 days after injury, is a subpial and periventricular accumulation of astrocytes and occasional groups of blood vessels; elsewhere glial and neuronal processes traverse the wound obliterating all signs of the original lesion. After 8 days
post natum
, scar tissue is deposited. The scar first appears in the superficial cortex as fibroblasts and macrophages invade from the meninges. With increasing age at injury, these cells penetrate more deeply and, after 16 days
post natum
at injury, the entire lesion contains these cells. Concomitantly, a glia limitans is formed over the walls of the lesion, firstly in the superficial cortex continuous with the glia limitans externa, and successively in the deeper cortex, white matter and corpus striatum as the meningeal fibroblasts and macrophages invade these regions. In the developing cerebrum, injured before 8 days
post natum
, the failure to form a scar is unrelated to the maturity of the astrocytes and fibroblasts, because both interact to regenerate the glia limitans externa. The development of a scar, in animals injured after 8 days
post natum
, is correlated with the failure of both axonal and dendritic regeneration. Because there are few oligodendrocytes, and no myelin, it appears that inhibition of axonal and dendritic growth is linked to scar formation, and not to putative inhibitory substrates such as those on the surface of oligodendrocytes, CNS scarring may be initiated by the invasion of fibroblasts and macrophages from the meninges into the injured neuropile. The possible reasons why these mesenchymal cells fail to penetrate before 8 days
post natum
are discussed.