Axonal transport of phospholipids labelled by lumbosacral spinal cord injection of [3H]choline has been studied in normal and injured sciatic nerves of the rat. 2. The appearance of labelled material in progressively increasing amounts in the sciatic nerve following spinal cord injection was consistent with a maximum velocity of axonal transport of about 20 mm/hr. There was also evidence of substantial amounts of labelled phospholipids being transported at much slower velocities. 3. In sciatic nerves injured by crushing there was an accumulation of labelled phospholipid immediately proximal to the crush. The accumulation was progressive with time. There was also an increase of labelled phospholipid in all the more proximal segments of the crushed nerves; this reached a maximum of about twice that in uncrushed nerves at 10 hr. after spinal cord injection. 4. The labelled phospholipid was shown to be about 80-90% phosphatidylcholine both in uncrushed and crushed nerves. 5. The nature of the mechanism of this very rapid response of neurones to peripheral injury did not appear to be due to loss of 'information' from the periphery or action potentials initiated at the site of injury. The phenomenon has been further investigated by injection of drugs into the injured or control nerves. KCl injected at (but not proximal to) the site of injury was effective in blocking the injury response providing it was injected between a few minutes before or up to 30 min after the time of injury. Injection of either tetrodotoxin or local anaesthetic was as effective as injury in increasing the amount of labelled phospholipid transport. 6. These results suggest that the occurrence of an injury in a distant process of a neuron can be signalled retrogradely to the cell body by a mechanism involving a signal velocity of at least 140 mm/hr.
