Twenty-five mongrel dogs were subjected to isolated cerebral hypoxia or noncerebral systemic hypotention to create the congestive pulmonary lesions of the shock lung syndrome (SLS). Eleven of the experimental dogs were pretreated with 5,5-diphenylhydantoin (DPH). Prophylactic DPH protects the lung from the injury that is a consequence of hypoxic cerebral perfusion in the dog, but does not afford protection from pulmonary damage caused by isolated, noncerebral systemic hypotension. DPH confers this protection on the brain; there is no evidence that DPH exerts this protective effect by an action on the pulmonary parenchyma directly or on other tissue in the body.