a gram negative human bacterial pathogen haemophilus influenzae expresses a truncated endotoxin known as lipooligosaccharide (los). recent studies on h. influenzae los have highlighted its structural and compositional implications on bacterial virulence; however, the role of los in the activation of innate and adaptive immunity is poorly understood. thp-1 monocytes were stimulated with either lipopolysaccharide (lps) from e. coli or los compounds derived from eagan, rd, and rd lie lips a h. influenzae strains. cell surface expression of key antigen-presenting, co-stimulatory, and adhesion molecules, as well as gene expression of some cytokines and pattern recognition receptors were studied. eagan and rd los had a lower capacity to induce the expression of the pro-inflammatory molecules, icam-1, cd40, cd58, tnf-a, and il-lp compared to lps. in contrast, antigen presenting (hla-abc, hla-dr) and co-stimulatory (cd86) molecules, and the pattern recognition receptor, nod2, were similarly upregulated in response to los and lps. los from a mutant rd strain (rd licllpsa) consistently induced higher expression of innate immune molecules than the wildtype los suggesting the importance of phosphorylcholine and/or oligosaccharide extension in cellular responses to los. an los compound with a strong ability to upregulate antigen-presenting and co-stimulatory molecules combined with a low proinflammatory activity may be considered as a vaccine candidate to immunize against h. influenzae.