That animals may be rendered tolerant to the various effects of bacterial lipopolysaccharide (LPS) affords a unique opportunity to study the possible role of endotoxin in the pathogenesis of byssinosis. Protein free LPS was isolated from Erwinia herbicola for aerosol studies on control, nontolerized and previously tolerized (single i.p. injection of 0.1 LD(50) LPS 48 hours prior to aerosol) male Syrian golden hamsters. LPS aerosol (effective concentration 0.004mg/m³) was administered for 5 hours. Six hours post exposure, lungs were processed for light and electron microscopic analysis. Ultrastructural alterations included septal capillary endothelial swelling and bleb formation in both tolerized and nontolerized hamsters. Platelet aggregates and abundant profiles of polymorphonuclear leukocytes (PMNS) were seen in septal capillaries of nontolerized hamsters exposed to LPS aerosol. Using standardized point count morphometry, distal lung alterations were analyzed quantitatively in control (no LPS treatment but subjected to 5 hour saline aerosol) and LPS aerosol-Exposed (tolerized and nontolerized) hamsters. Both the volume density and the number of profiles of PMNs in septal capillaries were increased in lungs of nontolerized but not in control and tolerized animals. The volume density of platelets was also higher in the nontolerized LPS aerosol-exposed group vs the other groups. The above changes seen at 6 hours post aerosol were not found in similarly treated animals 24 hours after aerosol indicating recovery to control morphology. Prior tolerization provided protection from the PMN and platelet changes seen in nontolerized animals. However, lungs of tolerized animals given LPS aerosol showed decreased pulmonary diffusion capacity and increased thickness of air-blood barrier when compared to the other two groups.