Schwann cell precursors in embryonic nerves rely for survival on signals from the axons they associate with. A major component of this signal is beta neuregulin. While it can be argued that such paracrine axonal regulation makes biological sense in embryonic nerves, such an arrangement would be problematic postnatally, since nerve damage would then lead to Schwann cell death with adverse consequences for regeneration; in fact, transection of older nerves is not accompanied by a detectable increase in Schwann cell death. Our evidence indicates that this is, at least in part, due to the ability of Schwann cells to support their own survival by autocrine circuits. These circuits are not present in Schwann cell precursors. We have identified insulin-like growth factor, neurotrophin-3 and platelet-derived growth factor-BB as components of the autocrine Schwann cell survival signal.