We have previously reported that antidepressants such as desipramine (DMI) induce axonal regeneration of brain noradrenergic neurons. In the present experiments, the role of phospholipase A2 (PLA2) in the regeneration of brain noradrenergic axons was studied. Symmetrical sites of the rat frontal cortex were pretreated with 6-hydroxy-dopamine (6-OHDA). Then, the same cortical site of one hemisphere was infused with DMI, while the corresponding site of the other hemisphere was infused with DMI plus 4-bromphenacyl bromide (BPB), a PLA2 inhibitor. The DMI-induced axonal regeneration was attenuated by BPB, while the PLA2 activator melittin induced the regeneration of noradrenergic axons. These findings suggest that activation of PLA2 is involved in the regeneration of brain noradrenergic axons.