The present study was designed to find out whether the prolonged administration of imipramine (IMI) or electroconvulsive shock (ECS) influences levels of endogenous enkephalins in the nucleus accumbens (NAS) and the ventral tegmentum (VTA) of the rat. Ressults indicate that treatment with IMI as well as with ECS has a profound effect on the levels of enkephalins in both structures. In the NAS both treatments lead to an increase in the levels of endogenous enkephalins and this effect is accompanied by an increase in mRNA coding for proenkephalin (measured by in situ hybridization) in this structure, indicating the enhancement of biosynthesis of endogenous enkephalinergic peptides following antidepressant treatment. The results are discussed in the light of the hypothesis concerning the influence of endogenous enkephalins on mesolimbic dopamine neurons, the activity of which plays a crucial role in the etiology of depression.