RESULTS: Pharmacologic ascorbate (vitamin C) is a pro-drug that produces detectable steady-state concentrations of hydrogen peroxide (H2O2) in extracellular fluid but not blood. At concentrations that are safely and easily achievable in humans, pharmacologic ascorbate reduced or eliminated infectivity of influenza A viruses H3N2, H1N12009, and H1N12009 oseltamivir-resistant in vitro, effects mediated by H2O2. In vivo, pharmacologic but not oral ascorbate treatment reduced lung viral titers in infected mice 10-100 fold, and prevented weight loss and death. Microscopic examination of lung from infected animals, with blinded evaluation, revealed normal or nearly normal tissues from treated animals, compared to unambiguous inflammatory changes in controls. Pharmacologic ascorbate is a promising new treatment agent for influenza and deserves clinical exploration.