Electroconvulsive therapy (ECT) can be effective in patients with depression resistant to pharmacologic medication. We report that serum levels of glial cell-line derived neurotrophic factor (GDNF) were increased following ECT of patients with drug-resistant depression. When patients were sub-classified into ECT responders and non-responders, serum GDNF levels were significantly increased (58%) in responsive patients following ECT. No significant increase was seen in non-responders. These results suggest that successful ECT may be associated with elevated serum GDNF levels.