The lung damage resulting from smoke inhalation is an important determinant of morbidity and mortality in thermally injured patients. We hypothesized that the degree of pulmonary microvascular damage seen with smoke inhalation could be affected by whether the smoke insult preceded or followed thermal injury. Fifteen chronically instrumented sheep were divided into two groups: seven were given a 40% 3rd-degree flame burn and then insufflated with smoke (smoke after burn group); eight were insufflated with smoke and then given thermal injury (smoke before burn group). Lung lymph flow and wet/dry weight ratio were significantly higher in smoke before burn group animals. We conclude that lung damage is minimized when thermal injury precedes smoke inhalation injury.