Taurine is one of the most abundant free amino acids in the brain. In a number of studies, taurine has been reported to activate glycine receptors (Gly-Rs) at moderate concentrations (Ն100 M), and to be a weak agonist at GABA A receptors (GABA A -Rs), which are usually activated at high concentrations (Ն1 mM). In this study, we show that taurine reduced the excitability of thalamocortical relay neurons and activated both extrasynaptic GABA A -Rs and Gly-Rs in neurons in the mouse ventrobasal (VB) thalamus. Low concentrations of taurine (10 -100 M) decreased neuronal input resistance and firing frequency, and elicited a steady outward current under voltage clamp, but had no effects on fast inhibitory synaptic currents. Currents elicited by 50 M taurine were abolished by gabazine, insensitive to midazolam, and partially blocked by 20 M Zn 2ϩ , consistent with the pharmacological properties of extrasynaptic GABA A -Rs (␣42␦ subtype) involved in tonic inhibition in the thalamus. Tonic inhibition was enhanced by an inhibitor of taurine transport, suggesting that taurine can act as an endogenous activator of these receptors. Taurine-evoked currents were absent in relay neurons from GABA A -R ␣4 subunit knock-out mice. The amplitude of the taurine current was larger in neurons from adult mice than juvenile mice. Taurine was a more potent agonist at recombinant ␣42␦ GABA A -Rs than at ␣12␥2 GABA A -Rs. We conclude that physiological concentrations of taurine can inhibit VB neurons via activation of extrasynaptic GABA A -Rs and that taurine may function as an endogenous regulator of excitability and network activity in the thalamus.