Changes in ectopic discharges from axons in an injured nerve were examined while agents that interact with ion channels were applied to the site of the nerve injury. Tetraethylammonium (TEA) greatly facilitated spontaneous ectopic discharges or evoked ectopic firing in previously silent axons. Tetrodotoxin, an Na+ channel blocker, completely blocked spontaneous discharges. Verapamil, La3+, and Mn2+, agents that interact with Ca2+ channels, blocked spontaneous discharges and depressed the responses evoked by TEA, noradrenaline and high concentration of K+. Increasing Ca2+ levels facilitated ectopic discharges and this effect was blocked by La3+ and Mn2+. Normal axons (from uninjured nerves) were insensitive to all the effects seen in the axons from the injured nerve. These results suggest that following nerve injury the membrane of the regenerating sprout contains new ion channels, particularly Ca2+ channels, and that these channels are responsible for the generation of ectopic discharges.