Intravenous administration of methyl linoleate hydroperoxide (MLH) uniformly resulted in extensive damage to septal wall components of the rat lung; the severity of these changes paralleled the administered dosage. The target cell of injury appeared to be the capillary endothelial cell. Destructive changes within the plasma membrane suggested that the major toxic effect of MLH was directed against membranous structures. Ultrastructural analysis showed that these effects were more severe in the vitamin E-deficient animals. Secondary changes were characterized by interstitial and alveolar edema, and degenerative changes within alveolar pneumocytes. Reparative proliferation of type 2 pneumocytes first became evident in animals that survived two days. These observations provide an insight into the susceptibility and sequential damage to pulmonary tissue by hydroperoxides and serve as a guide for investigations of the toxic effects of other oxidants on lung.