This work demonstrates that the natural killing function of the innate immune system is affected in psychiatric disorders related primarily to serotonergic pathways in the CNS rather than to psychiatric disorders which involve mainly dopaminergic pathways. Only depressive patients demonstrated low natural killer (NK) cell activity, which is inversely correlated to the intensity of depression and could be reversed by serotonin selective re-uptake inhibitors concomitant with clinical improvement. This phenomenon is absent in Parkinson's and schizophrenic patients, in whom no reduction in NK activity was observed. Also, no effect on NK activity could be demonstrated following the specific respective treatments by dopamine (D-2) blockers or agonists. (C) 1999 Elsevier Science B.V. All rights reserved.