The influence of plasma zinc concentration on the rate of zinc transport into the brain was examined using an in vitro model of the blood-brain barrier. The model was constructed by culturing porcine brain capillary endothelial cells on porous membrane filters suspended between two chambers of fluid, representing the capillary lumen and the cerebrospinal fluid of the brain. A relatively narrow range of zinc concentrations (2-30 mol/L) was employed in order to examine the most physiologically relevant situation, obtained by diluting the serum or adding ZnCl 2 . The results consistently found that the rate of zinc transport across the blood-brain barrier was similar (P > .05) between 10 and 26 mol zinc/L; the rate was slower (P < .05) at zinc concentrations below 7 mol/L and faster (P < .05) above 30 mol zinc/L. These results demonstrate that the blood-brain barrier is highly restrictive to zinc. Zinc enters the brain at a constant rate within the range of plasma zinc concentrations that occur in healthy individuals. Outside this range, zinc transport was significantly altered. The zinc transport process was highly selective for zinc, since none of the analogous minerals could effectively compete with it. The zinc transport process does not require energy, since metabolic inhibitors did not influence the transport rate.