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The biological half-life of manganese and some factors influencing it have been studied in man. The disappearance of manganese from the body in normal subjects is described by a curve having two exponential components. An average of 70% of the injected material was eliminated by the "slow" pathway. The half-time characterizing this component showed a small variation in normal subjects and had an average value of 39 days. The half-time for the "fast" component also showed a small variation and had an average value of 4 days. In a normal subject presumed to have a low manganese intake due to a voluntary low caloric intake, the percentage eliminated by the slow pathway increased to 84% and the half-time characterizing the pathway increased to 90 days. The half-time of the "fast" component was the same as for the normal group. 2 months after initiation of the study in this subject, a large "flushing" dose of manganese markedly increased the elimination rate which was described by a single exponential curve.A mildly iron-deficient subject showed a marked decrease in the percentage of manganese eliminated by the "slow" pathway accompanied by a less dramatic decrease in the half-time characterizing this pathway. Oral iron therapy, which corrected the mild anemia, caused a decrease in the elimination rate and the altered curve was described by a single exponential component. Preloading two subjects with manganese resulted in a great decrease in the fraction eliminated by the "slow" pathway with less effect on the half-time. The subject with the largest preloading dose showed no "slow" component at all. Observations on the red cells of some of these subjects showed that a small but definite fraction was incorporated into the erythrocytes. In the mildly iron-deficient subject, our observations suggest an interrelationship between manganese and iron metabolism.