Recent research in animals indicates that the generalized regulation of cortical activity that is represented by activation of the electrocorticogram is dependent on ascending cholinergic and serotonergic projections. The effect of the activity of these systems is correlated with concurrent motor activity in a detailed and specific manner. Combined blockade of central cholinergic and serotonergic function results in impaired cerebral control of behavior, i.e., a dementia-like syndrome. Previous concepts, which held that electrocortical activation is mediated via a reticulo-thalamo-cortical pathway and that it is related primarily to arousal, vigilance, and the sleep-waking cycle appear to be incomplete or erroneous.