Zinc uptake and turnover was measured in nine brain regions, choroid plexus, arachnoid, and cerebrospinal fluid during a 28-day period following a single dose of 65Zn in rats fed Zn-adequate diets. Zinc entry into brain was slow with maximal 65Zn uptake (0.5% of administered dose) occurring between 5 and 14 days in contrast to its rapid metabolism in plasma and nonneural tissues. The brain stem, at the level of the caudal IV ventricle, had the highest rate of initial 65Zn uptake of any brain region. In general, turnover was most rapid in periventricular regions and least in the hippocampus. Relative to plasma, the choroid plexus concentrated 65Zn whereas 65Zn was undetectable in the cerebrospinal fluid after day 1. To determine if specific brain regions were particularly sensitive to changes in Zn status, 65Zn metabolism was measured in Zn-deficient rats and compared with ad libitum- and pair-fed controls. Zinc deficiency was associated with increased 65Zn retention by all brain regions; however, the effect was greatest in optic nerve and choroid plexus. The results of this study suggest that a formidable barrier to Zn entry into brain exists but is under homeostatic control, increasing net Zn uptake during dietary deficiency. Moreover, the choroid plexus may participate in cerebral Zn homeostasis, possibly by transporting Zn out of the cerebrospinal fluid compartment.