The influence of intravenous and oral histidine administration on zinc metabolism in the rat has been investigated. Acute studies: histidine (250 mg/hr) was given by constant intravenous infusion to rats with paired control animals receiving diluent alone. During the hour preceding histidine the urinary zinc excretion averaged 0.435 +/- 0.37 (SE) microng/hr. During the hours of histidine infusion the urinary zinc excretion averaged 7.58 +/- 0.97, 20.21 +/- 2.07, and 16.78 +/- 1.90 microng/hr. These values were all higher than the prehistidine infusion value and higher than in the rats receiving diluent alone. Plasma zinc at the end of the infusion was 76 +/- 5 microng/100 ml compared to control levels of 110 +/- 9 microng/100 ml, P less than 0.001. Chronic studies: histidine (500 mg/day) was given by gavage for 43 days to rats. Urinary zinc excretion in histidine treated rats was 3 to 6 times that of controls throughout the study. Despite this there was no difference in the plasma, testicular, or kidney zinc content. No histological lesions of zinc deficiency were noted in the esophagus. In conclusion, histidine increased urinary excretion in the rats whether administered orally or parenterally. Evidence for zinc deficiency, however, was not apparent after 43 days of histidine administration.