Inhalation injury was produced in sheep that were chronically prepared for study. The injury was induced by insufflating them with smoke from burning cotton cloth. One group of animals was treated with the oxygen-free radical scavenger dimethylsulfoxide (DMSO) and heparin. Another group received heparin treatment alone, and a third was untreated. The drugs were nebulized into the tracheostomy at 4-hr intervals beginning 1 hr after injury. Following the inhalation injury, lung lymph flow and extravascular lung water measured by thermal-dye dilution technique were both increased. These elevations were associated with minor increases in pulmonary artery pressure, and, thus, since the lymph to plasma protein ratio was unchanged, this increased extravascular fluid formation was probably the result of an elevated microvascular permeability. These changes were associated with a reduction in alpha 2 macroglobulin antiprotease activity. The treated groups showed much smaller responses to the inhalation insult. This was especially true in the animals that received the DMSO. These findings support the concept that oxygen free radicals are responsible for the pulmonary edema associated with inhalation injury.