Microprobes bearing immobilized antibodies to the C-terminus of neuropeptide Y were used to measure the release of this neuropeptide in the spinal cords of rats with a unilateral peripheral neuropathy and in sham-operated animals. All neuropathic animals showed the characteristic behavioural syndrome and were studied at 14 days postsciatic nerve loose-ligation. An extensive spontaneous release of immunoreactive neuropeptide Y was detected in the spinal cords of the neuropathic rats and, compared to sham-operated rats, a new zone of release was found in the deep dorsal horn. Electrical stimulation of large diameter primary afferents proximal to the nerve ligature produced widespread release of neuropeptide Y in the dorsal horn which persisted for up to 1 h poststimulation. It is possible that ectopic impulses arising in the injured nerve were responsible for the spontaneous central release of neuropeptide Y and this neuropeptide may play a role in the central response to peripheral nerve injury.