The experimentally induced smoke inhalation injury in sheep is in many respects similar to that observed in smoke-injured humans. Our sheep model allows us to describe a sequence of morphologic changes that may be divided into four fairly discrete although overlapping phases. The magnitude of the destructive process and the length and characteristics of each phase are related to the severity of the injury and the superimposed complications. The availability of this animal model may allow the experimental manipulation of each of the four described phases to investigate physiopathologic and therapeutic implications toward the prompt normalization of pulmonary function.