Histidine has been reported to affect body zinc status by increasing urinary zinc excretion. The effects of experimental histidinemia on distribution of 65Zn in anesthetized rats were studied. Infusion of L-histidine at a rate sufficient to raise plasma concentrations to approximately 2 mM for 6 h starting 48 h after a single intraperitoneal 65Zn injection did not alter 65Zn activities in a variety of tissues when compared with anesthetized uninfused animals. However, plasma 65Zn and erythrocyte 65Zn were decreased, and liver 65Zn was increased. If 65Zn was injected intravenously during histidine infusion, net accumulation of zinc by some tissues was increased, but uptake by others was reduced relative to uninfused animals. In all cases, however, uptake expressed relative to plasma 65Zn levels was increased when allowance was made for the more rapid fall in plasma 65Zn during histidine infusion. Similar infusions of D-histidine produced quantitatively similar effects. Since enzymatic mechanisms and amino acid carriers would be expected to show stereoselectivity, such processes are unlikely to be involved in the zinc distribution changes described. The possibility of zinc transport by a hitherto unidentified carrier is discussed. These experiments confirm that histidinemia can affect zinc status, but any associated changes in urinary zinc excretion do not seem adequate to account for the tissue changes found.