Two microbial factors of interest in the pathogenesis of byssinosis, lipopolysaccharide (LPS) and N-formyl methionyl peptides (NFMP) have been compared immunotoxicologically. NFMP has been shown to be unable to cause Limulus lysate gelation and to be nonpyrogenic, unlike LPS. Whereas aerosol challenges with LPS result in peripheral leukocytosis within 30 min, similar challenges with NFMP produce a leukopenia. Finally, aerosol challenges with these two materials evoke distinctly different patterns of inflammatory cell response into the airways. It is concluded that cotton dust investigators should have little trouble distinguishing the in vivo effects of these agents and that those produced by LPS more closely resembly those known to be produced by cotton dust.