Nitric oxide has been identified as having a role in synaptic transmission in the central nervous system. In the ventrobasal complex of the thalamus (VB), the precursor of nitric oxide synthesis, L-arginine, causes enhancement of excitatory amino acid responses and somatosensory transmission. In this study, the nitric oxide donors sodium nitroprusside, 3-morpholinosydnonimine and S-nitrosoglutathione were applied to VB relay neurons by iontophoresis and responses of single neurons were recorded extracellularly. Sodium nitroprusside caused selective inhibition of responses to NMDA, probably mediated by a by-product, ferrocyanide, as described in previous studies. 3-Morpholinosydnonimine and S-nitrosoglutathione, however, caused potentiation of responses to sensory stimuli and to excitatory amino acids. In contrast, glutathione in both its reduced and oxidized forms reduced such responses, and this suggests that the potentiating effect of S-nitrosoglutathione could be due to nitric oxide production. These results are consistent with the hypothesis that nitric oxide may have a local modulatory role in the thalamus. Data are presented which suggest that glutathione may have a negative modulatory influence on neurotransmission and excitatory amino acid responses in the ventrobasal thalamus.