In continuing morphometric studies designed to assess the role of inflammatory mediators in lung injury following endotoxin inhalation, a specific, plateletactivating factor inhibitor (RP 48740) was used to determine those contributions due to this mediator. Infection-free hamsters were exposed to either saline or standard aqueous LPS aerosols (4 ug/m³ for 5 hr) and compared with similarly exposed groups of hamsters treated with PAF inhibitor. Since it was found that the use of this inhibitor blunted nearly all of the known inflammatory effects of LPS inhalation, it was concluded that PAP is the major mediator of endotoxin injury. A significant additional observation was that the use of the drug in itself initiated tissue changes, so it should be used cautiously. In separate, but related studies it was found that inhalation of endotoxin-containing bacteria results in a small, but significant amount of pulmonary edema.