1. Epinephrine is widely distributed in brains of various species throughout phylogeny but maintains its localization to hypothalamus and brainstem/medulla in all species studied. 2. A general decrease in brain epinephrine content is observed phylogenetically beyond fishes with wide variation within species. 3. The cellular localization of epinephrine forming enzyme is dissociated from epinephrine stores in hypothalamus where epinephrine appears to be primarily a hormone. 4. Three proposed functional pools of epinephrine are described. Synthesis of a hormonal pool and a second, perhaps nonfunctional, pool co-stored in noradrenergic terminals in the forebrain occurs extraneuronally and is probably inhibited acutely in the presence of high corticosteroids due to inhibition of uptake 2. Synthesis of epinephrine in the neuronal pool found primarily in the medulla may be enhanced due to increased PNMT activity in the presence of elevated corticosteroids. 5. Phylogenetic and pharmacological data suggest that epinephrine may play an important role in tonic regulation of the level of arousal, reward and sensitivity to environmental stimuli in mammals.