To examine the mechanism whereby asbestos fibers penetrate tracheal epithelial cells, we exposed rat tracheal explants to amosite asbestos alone, or with varying concentrations of substances that scavenge active oxygen species (catalase and superoxide dismutase) or prevent formation of active oxygen species (deferoxamine). All three agents decreased asbestos fiber uptake in a dose-response fashion, but no agent provided complete protection against fiber penetration. We conclude that uptake of amosite asbestos fibers is mediated in part by active oxygen species (most likely OH.), but that other mechanisms of fiber uptake must also exist.