A study was undertaken to define the inflammatory mediators that might be involved in the tissue changes induced by endotoxin inhalation. Highly purified lipopolysaccharide (LPS) prepared from Enterobacter agglomerans was converted into defined salt forms by electrodialysis to make the material particle free and in a physical state that would facilitate comparison with LPS preparations from other species. Part of the product was further treated with 0.25 M NaOH to render the lipid A non-toxic. Groups of hamsters received standard 5 h aerosols of each preparation and were bled 6 h later for assay of PGF(2a), PGE, and TBX(2). PGE production was significantly elevated in animals receiving treated LPS, but was normal in animals receiving the unaltered material. Similarly, thromboxane B(2) levels were significantly elevated in animals exposed to treated LPS, but not untreated material. PGF₂, production was unaffected by either material. Although chemical treatment obviously affected the biologic responses to LPS, it was clear that LPS inhalation in modest doses does affect important mediators of pulmonary function and these alterations last for periods well beyond the time of insult.