Tannins are believed to function as plant defenses against caterpillars, in part, as a result of their oxidation in the midgut lumen. One putative mode of action that has not been examined in leaf-feeding larvae is oxidative stress in midgut tissues that results from tannin oxidation in the midgut lumen. The test species used in this study, Malacosoma disstria Hübner (Lasiocampidae), is known to have higher levels of phenolic oxidation in its midgut contents when it consumes the oxidatively active leaves of sugar maple (Acer saccharum Marshall) than when it consumes the leaves of red oak (Quercus rubra L.). This study tested the hypothesis that increased phenolic oxidation in the midgut lumen of M. disstria is associated with increased oxidative stress in its midgut tissues. Three markers (oxidized ascorbate:total ascorbate, oxidized glutathione:total glutathione, and oxidized proteins) were measured in larvae fed either sugar maple or red oak leaves. In addition, we examined whether superoxide dismutase (SOD) activity might be a useful inducible marker of oxidative stress in M. disstria midgut tissues. Three of the markers indicated that significantly higher levels of oxidative stress were produced in the midgut tissues of M. disstria that fed on sugar maple than on red oak. However, SOD activity did not differ between sugar maple- and red oak-feeding larvae. This study is the first to show a link between phenolic oxidation in the midgut contents of caterpillars and oxidative stress in their midgut tissues.