Pathogenic microbes require Fe2+ and Zn2+ for growth and proliferation. Upon infection, microbes produce proteins, called sidephores, designed to strip serum divalent metals away from host proteins. Higher eukaryotes respond to infection by increasing the expression of proteins that sequester serum iron away from bacteria. As a result, host plasma Fe2+ levels decrease during the initial phases of infection. This study was conducted to determine if the American alligator, an ancient reptile, exhibits the same innate immune mechanism to protect against in vivo microbial proliferation. Intraperitoneal injection of juvenile captive alligators with bacterial lipopolysaccharide resulted in a time-dependent decrease in plasma Fe2+. Plasma Fe2+ levels decreased to 89% of control levels at 6 hrs post-injection and decreased to 81% by 12 hrs. Plasma Fe2+ concentrations increased to 87% of control values at 24 hrs, and still remained at 88% at 48 hrs. Alligators injected with pyrogen-free saline did not exhibit statistically significant changes in plasma Fe2+ concentrations at any time point observed. In contrast, serum Zn2+ and Cu2+ remained unchanged relative to untreated and saline-injected controls. To insure that the decrease in plasma Fe2+ was not due to depletion caused by the repeated bleedings during the course of the experiment, another experiment was conducted in which blood was drawn only once (24 hr time point). The same results were observed, as plasma Fe2+ fell to 70% of untreated control animals, while Zn2+ and Cu2+ levels remained unchanged. Saline-treated animals did not exhibit reduced Fe2+, Zn2+, or Cu2+ levels.