The mechanism by which iodide cures sporotrichosis was postulated to be an improvement in phagocyte-mediated killing of the causal fungus, Sporothrix schenckii. We found that both neutrophils and monocytes could readily kill the fungus and that killing could be blocked by adding inhibitors of oxidative metabolism. Iodide, administered to four volunteers for 1 week, raised their serum iodide level 213-fold but failed to improve killing of S. schenckii by their neutrophils or monocytes in a killing assay in vitro. Furthermore addition of iodide directly to neutrophils at concentrations as high as 100 microM did not augment killing. The mechanism by which iodide acts remains obscure.