It is hypothesized that the cholinergic and monoaminergic neurons of the brain from a global network. What is meant by a global network is that these neurons operate as a unified whole, generating widespread patterns of activity in concert with particular electroencephalographic states, moods and cognitive gestalts. Apart from cholinergic and monoaminergic global systems, most other mammalian neurons relay sensory information about the external and internal milieu to serially ordered loci. These "serial" neurons are neurochemically distinct from global neurons and commonly use small molecule amino acid neurotransmitters such as glutamate or aspartate. Viewing the circuitry of the mammalian brain within the global-serial dichotomy leads to a number of novel interpretations and predictions. Global systems seem to be capable of transforming incoming sensory data into cognitive-related activity patterns. A comparative examination of global and serial systems anatomy, development and physiology reveals how global systems might turn sensation into mentation. An important step in this process is the permanent encoding of memory. Global neurons are particularly plastic, as are the neurons receiving global inputs. Global afferents appear to be capable of reorganizing synapses on recipient serial cells, thus leading to enhanced responding to a signal, in a particular context and state of arousal.