The neurophysiology and neuroanatomy of the thalamus have been extensively studied in a variety of species and sensory systems. The identity of the neurotransmitter(s) which mediate the excitation from ascending sensory afferents on to thalamic relay neurons is, however, still unclear, although it appears to be a substance which is a ligand for excitatory amino acid receptors, as the responses of ventrobasal thalamus neurons to natural stimulation of somatosensory afferents arising from the mustachial vibrissae of the rat are mediated by ionotropic excitatory amino acid receptors, when stimulation is performed using an air-jet directed at the vibrissa receptor field. In an effort to determine the transmitter of these sensory afferents, we have attempted to detect the release of amino acids in the ventrobasal thalamus in vivo upon such stimuli. We have thus used a similar natural stimulation protocol, together with push-pull perfusion and recording in the ventrobasal thalamus, and we describe the release of the amino acid, arginine, in this brain area following physiological stimulation of afferents. Furthermore, we show that application of L-arginine on to thalamic relay neurons can facilitate sensory synaptic transmission, possibly via the synthesis of the diffusable messenger, free radical gas, nitric oxide. This may represent a novel, local positive-feedback, modulatory system which could enhance the responsiveness of thalamic neurons to sensory input.