Recent studies suggest that lung lesions occurring in inhalation injury result from actions of oxygen-free radicals released from polymorphonuclear leukocytes marginating in the pulmonary microcirculation and tracheobronchial region. Peroxide and hydroxyl ions have been implicated as mediators in the increased microvascular permeability and pulmonary edema noted after inhalation injury. In this study we evaluated the use of an O2-free radical scavenger, dimethylsulfoxide (DMSO), and heparin in the treatment of smoke inhalation. Ewes (N = 26) that had been surgically prepared five days earlier were insufflated with smoke from burning cotton. There were four groups: controls (n = 7), DMSO (n = 6), heparin (n = 6), and DMSO plus heparin (n = 7). All animals were given ventilatory support to maintain their PO2 above 60 mmHg and their PCO2 below 45 mmHg. There was a significant difference in survival rates between groups. By 72 hours all seven of the control group were dead. All animals in the DMSO plus heparin group survived, four of the DMSO group died, and two of the heparin group died. Lung lymph flow was not as high in the DMSO plus heparin group as in the heparin-only group. DMSO was proved effective in reducing the lung injury associated with smoke inhalation.