In a previous study we have shown that, in response to electrical stimulation, there is a substantial release of noradrenaline (NA) from the sympathetic nerve terminals of the rat thymus which is of axonal, vesicular origin. In the present study neurochemical evidence was obtained that the release of NA is subject to presynaptic modulation. This modulation operates through stimulation of alpha 2B-adrenoreceptors, N-nicotinic, P1-purinergic and prostaglandin E2 presynaptic receptors. Through these receptors the release of NA, i.e., the message from the central nervous system to the thymus, can be affected by endogenous ligands or drugs. A novel, potent and highly selective competitive antagonist of the alpha 2-adrenoreceptor, CH-38083, significantly enhanced the release of NA, suggesting that its release in the thymus is under tonic inhibitory control exerted by endogenously released NA. Since adrenoreceptors on thymocytes involved in the modulation of certain thymocyte functions have recently been described, it is suggested that the presynaptic modulation of the release of NA in the thymus is involved in neuro-immune communication.