Technical Abstract: Molybdenum is an essential mineral in the human diet and is toxic when intake is excessive. Data on which to base dietary recommendations, especially for excessive intake for humans, is limited. The objective of this study was to determine physiologic adaptations that occur when humans are exposed to a wide range of molybdenum intake levels. Four males consumed each of five daily molybdenum intakes of 22, 72, 121, 467, and 1490 microg/d for 24 days each. During each treatment period oral and intravenous doses of 100-Mo and 97-Mo were administered. Serial plasma, urine, and fecal samples were analyzed for labeled and unlabeled molydenum. Compartmental modeling was used to determine rates of distribution and elimination at each dietary intake level. Three pathways were sensitive to daily molybdenum intake: the fraction of plasma molybdenum excreted into urine increased with increasing molybdenum intake, the fraction of plasma molybdenum deposited into tissues decreased with increasing intake, and absorption efficiency was greater at higher intakes. Kinetic analysis suggested a daily intake of 115-120 microg/day would be required to maintain initial plasma molybdenum levels. Physiologic adaptations to changing molybdenum intakes identified here reveal how the body reduces the risk of molybdenum deficiency and toxicity.