The aim of the present study was to establish whether antidepressants (ADs) of potentially different chemical structure and mechanisms of action affected the phospholipase A2 (PLA2) activity in plasma membranes of the rat brain cortex. It was decided to evaluate the influence of imipramine (IMI), amitriptyline (AMI), fluvoxamine (FLU), mianserin (MIA) and tianeptine (TIA) on PLA2 activity after an acute and long-term (4 weeks) drug administration. To study the time-related effects of FLU on PLA2 activity, animals were treated for 1, 7, 14 and 28 days. The experiments were performed on male Wistar rats. The PLA2 activity was determined by the method of Strosznajder and Strosznajder as well as Jelsema with slight modifications. It was shown that ADs significantly changed the PLA2 activity in plasma membranes of the rat brain cortex and the effects depended on the dose, time of administration and the structure of the drug. Tricyclic ADs, both classic (IMI and AMI) as well as atypical (e.g. TIA) inhibited PLA2 activity. It seems that FLU was the only antidepressant, which induced either inhibition or activation of PLA2 depending on time of administration. It may be suggested that PLA2 appears to be a common target for drugs showing quite different mechanisms of action.