Neocortex network activity varies from a desynchronized or activated state typical of arousal to a synchronized or deactivated state typical of quiescence. Such changes are usually attributed to the effects of neuromodulators released in the neocortex by nonspecific activating systems originating in basal forebrain and brain stem reticular formation. As a result, the only role attributed to thalamocortical cells projecting to primary sensory areas, such as barrel cortex, is to transmit sensory information. However, thalamocortical cells can undergo significant changes in spontaneous tonic firing as a function of state, although the role of such variations is unknown. Here we show that the tonic firing level of thalamocortical cells, produced by cholinergic and noradrenergic stimulation of the somatosensory thalamus in urethane-anesthetized rats, controls neocortex activation and deactivation. Thus in addition to its well-known role in the relay of sensory information, the thalamus can control the state of neocortex activation, which may complement the established roles in this regard of basal forebrain and brain stem nuclei. Because of the topographical organization of primary thalamocortical pathways, this mechanism provides a means by which area-specific neocortical activation can occur, which may be useful for modality-specific sensory processing or selective attention.