Local injections of corticosteroids are frequently used in the treatment of regional pain. The rationale for this is not very clear, since an inflammatory cause of pain is rarely evident. There are few data on the effect of corticosteroids on nociception in experimental animals. However, corticosteroids have been found to suppress ectopic discharges from experimental neuromas and to have a short-lasting suppressive effect on transmission in normal C-fibers. In this study the influence of a locally applied depot form of a corticosteroid on neuropathic pain was investigated in a rat model. Peripheral mononeuropathy was induced with a chronic constriction injury to the left sciatic nerve. This procedure has previously been shown to produce various signs of disturbed sensibility, including heat hyperalgesia, mechanical allodynia, and mechanical hyperalgesia, indicating that a neuropathic pain-like condition has developed. The occurrence of neuropathic pain in these animals was confirmed with behavioral testing after 9 days. The site of injury was then reexposed and treated locally with either a depot form of a corticosteroid (methylprednisolone) or saline. The animals were then tested for another 11 days. The heat hyperalgesia and mechano-allodynia but not the mechano-hyperalgesia were depressed in the animals receiving the corticosteroid but not in those treated with saline. The effect remained during the whole 11-day test period. It is hypothesized that the corticosteroid acts by suppression of ectopic neural discharges from the injured nerve fibers.