Purified endotoxin from Salmonella Minnesota wild type bacteria has been found to cause an acute respiratory response in guinea pigs indistinguishable from that produced by purified endotoxin from Enterobacter agglomerans or Pseudomonas syringae, the major Gram negative bacterial species found in cotton dust. The pulmonary toxicity of this model lipopolysaccharide (S. minn. LPS) was compared with that of its Re mutant (ReLPS) and was found to be similar. In the present study, lipid A and monophosphoryl lipid A (MPL) were compared to the S. minn. LPS and its ReLPS by measuring the development of rapid shallow breathing in guinea pigs exposed for 6 hrs to aerosols of these materials. Pulmonary function was measured as animals breathed either ambient air or air containing 10% CO₂. When compared with lipid A at the same concentration, MPL was found to have no effect on tidal volume (VT) and frequency (f) immediately after and 18 hours post exposure. When comparing concentration-response relationships involving VT and f, measured 18 hrs postexposure with 10% CO₂, lipid A appeared to have less toxicity than either S. minn. LPS or ReLPS. Results indicate that absence of the phosphate group at the reducing end of the lipid A disaccharide of MPL removed its pulmonary toxicity.