GABAergic signaling is central to the function of the thalamus and has been traditionally attributed primarily to the nucleus reticularis thalami (nRT). Here we present a GABAergic pathway, distinct from the nRT, that exerts a powerful inhibitory effect selectively in higher-order thalamic relays of the rat. Axons originating in the anterior pretectal nucleus (APT) innervated the proximal dendrites of relay cells via large GABAergic terminals with multiple release sites. Stimulation of the APT in an in vitro slice preparation revealed a GABA(A) receptor-mediated, monosynaptic IPSC in relay cells. Activation of presumed single APT fibers induced rebound burst firing in relay cells. Different APT neurons recorded in vivo displayed fast bursting, tonic, or rhythmic firing. Our data suggest that selective extrareticular GABAergic control of relay cell activity will result in effective, state-dependent gating of thalamocortical information transfer in higher-order but not in first-order relays.