The neurotransmitter dopamine oil its own increased significantly TNF alpha and IL-10 secretion by resting normal-human T-cells, and induced similar to 5-fold elevation of the corresponding mRNA's, without affecting IFN gamma and IL-4. Using seven highly selective dopamine-receptor (DR) agonists and antagonists we found that TNF alpha-upregulation, evident after 24 h, was mediated by D3R and D1/D5R while IL-10-upregulation, evident after 72 h, was mediated by D2R and D1/D5R. We confirmed the expression of D2R and D3R in these human T cells. Dopamine's unique ability to trigger a selective secretion of either TNF alpha only (via D3R) or IL-10 only (via D2R) or both (via D1/D5R), differs front the robust and non-selective cytokine-secretion induced by 'classical, TCR-activation, and as such may have important beneficial or detrimental implications in various immunological and neurological diseases/injuries/cancers. (C) 2005 Elsevier B.V. All rights reserved.