Single unit studies indicate that increased activity in the cholinergic nucleus basalis (NB) correlates with behavioral activation and neocortical desynchronization. Lesions of the NB result in neocortical slow delta waves, similar to the action of antimuscarinic drugs, and the lesion releases the oscillation of GABAergic neurons in the reticular nucleus of the thalamus, resulting in high voltage neocortical spindles. Extensive damage of the thalamus does not produce slowing of neocortical activity but it abolishes neocortical spindles. We suggest that the NB plays a key role in neocortical activation by a) blocking the afterhyperpolarizations and accommodation in neocortical pyramidal neurons and b) suppressing the rhythm generation in the reticular nucleus-thalamocortical circuitry. We further suggest that the NB system may serve as a structural basis for the concept of the generalized activation described by Moruzzi and Magoun (1949).