The amino acids tyrosine and DL-threo-3,4-dihydroxyphenylserine (DL-threo-DOPS) were compared for their effectiveness in increasing central nervous system norepinephrine (NE) turnover in both saline and DSP-4 pretreated mice. NE was decreased significantly in cortex, hippocampus and cerebellum, and only slightly in hypothalamus and brainstem two weeks after a single intraperitoneal injection of the neurotoxin DSP-4. Levels of the major NE metabolite, 3-methoxyl-4-hydroxyphenylethylene glycol (MHPG), decreased in parallel in these five brain regions. Neither administration of tyrosine (250 mg/kg, as the ethyl ester, i.p.) nor DL-threo-DOPS (200 mg/kg, i.p.) affected regional NE concentration. However, after tyrosine administration, MHPG levels increased significantly in cortex in control mice and in cortex and hippocampus of DSP-4 pretreated mice. In all five brain noradrenergic regions MHPG level increased after DL-threo-DOPS administration and this increase was enhanced (approximately doubled) in DSP-4 pretreated mice. Thus, both amino acids may be useful as precursors of central NE when its level is depleted (e.g. following administration of DSP-4); DL-threo-DOPS producing a generalized increase in brain NE turnover, while increases following tyrosine are specific to those areas in which neuronal activity is increased i.e. cortex and hippocampus.