The present experiments demonstrate that: (1) activation of delta-opioid receptors by a highly selective agonist DSLET leads to immunosuppression, whereas the blockade of these receptors by enkephalin analog ICI 174864 produces immunostimulation; (2) the immunomodulating effect of delta-opioid receptors is mediated by central mechanisms involving the hypothalamus-hypophysis complex; (3) the postsynaptic 5-HT (serotonin) receptors of 5-HT-2 type are involved in the immunoinhibitory action of DSLET. On the other hand, the immunostimulating effect of ICI 174864 is realized with the participation of D-2 postsynaptic DA (dopamine) receptors. It has also been shown that thymus is implicated in the immunostimulating influence of ICI 174864. The data obtained are explained as a result of the interaction of the neuromediator and opioid peptidergic systems in neuroimmunomodulation.