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Tf protein levels in lung and bronchoalveolar lavage fluid did not change in iron deficiency despite increased plasma levels, suggesting that lung Tf concentrations are regulated by local synthesis in a manner independent of body iron status. Iron oxide exposure upregulated Tf mRNA in bronchial and alveolar epithelium, macrophages, and BALT, but protein was not significantly increased. In contrast, TfR mRNA and protein were both upregulated by iron deficiency. To examine potential interactions with lung Tf, rats were intratracheally instilled with<jats:sup>54<\/jats:sup>Mn or<jats:sup>59<\/jats:sup>Fe. Unlike<jats:sup>59<\/jats:sup>Fe, interactions between<jats:sup>54<\/jats:sup>Mn and Tf in lung fluid were not detected. Absorption of intratracheally instilled<jats:sup>54<\/jats:sup>Mn from the lungs to the blood was unimpaired in Belgrade rats homozygous for the functionally defective G185R allele of divalent metal transporter-1, indicating that this transporter is also not involved in pulmonary manganese absorption. Pharmacological studies of<jats:sup>54<\/jats:sup>Mn uptake by A549 cells suggest that metal uptake by type II alveolar epithelial cells is associated with activities of both L-type Ca<jats:sup>2+<\/jats:sup>channels and TRPM7, a member of the transient receptor potential melastatin subfamily. 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