Regenerating axons need proteins to grow and we explored whether a local supply is necessary. Crushed peroneal nerves were entubulated with silicone sleeves, plain or loaded with cycloheximide (CHX); some nerves were frozen to kill resident cells. When a plain sleeve was placed distal to the crush, axons regrew 5.0 mm in 3 days (pinch test), and 4.6 mm when the sleeve was placed around a frozen nerve (n.s). CHX administered distal to the crush reduced the elongation by approximately 58% (P < 0.01) in unfrozen or frozen nerves whilst its administration central to the crush was ineffectual. Immunostaining of nerves with GAP-43 gave similar values. Under the electron microscope, axonal sprouts were less frequent when CHX was used irrespective of the cellular or acellular condition of the nerve. Therefore, an inhibitor of protein synthesis reduces axonal regrowth, an effect mediated neither by parent neurones nor by resident cells. We propose that axons synthesize proteins.