Several findings have suggested that the neurotrophin BDNF could contribute to clinical efficacy of antidepressant treatments. The purpose of this study was to analyse if ECT operates a modulation of serum BDNF levels in a sample of drug resistant depressed patients. The results obtained show significantly higher serum levels of BDNF following ECT. More specifically, while no change occurred in the whole sample between T0 (baseline) and T1 (after ECT) (p=0.543) a significant increase has been identified at T2, one month after the end of ECT (p=0.002). However, the BDNF augmentation was evident even between T0 and T1 in a subgroup of patients who has low baseline BDNF levels. Although future researches are needed, the results herein presented show for the first time that ECT is associated with changes in serum BDNF and further support the possible involvement of BDNF in antidepressant therapies.