Evidence is presented that emotional stress in the mouse, guinea pig, and rat are associated with 10-30 per cent decrements in brain norepinephrine. This does not appear to be primarily a function of muscular activity and is probably a neurochemical concomitant of the 'emotional' upset. It is a generalized phenomenon that occurs in cortex, subcortex, cerebellum, hypothalamus, and brain stem, to approximately the same degree. Under these circumstances the concentration in brain of serotonin, gamma-aminobutyric acid, and dopamine remain stable. It appears that decreases of brain norepinephrine may be a component of a general response to intense, emotional distress.