The novel chemical structure of Porphyromonas (Bacteroides) gingivalis strain 381 lipid A was determined to be a glucosamine beta-(1-6) disaccharide 1-monophosphate acylated by 3-hydroxy-15-methylhexadecanoic acid and 3-hexadecanoyloxy-15-methylhexadecanoic acid at the 2- and 2'-positions, respectively. The absence of ester-linked phosphate at the 4'-position and fatty acids at the 3- and 3'-positions, and the presence of fatty acids possessing 16-17 carbon atoms are unique features, differentiating the lipid A from enterobacterial and other lipid As. These structural features may be related to its low endotoxic activity. Furthermore, P. gingivalis lipid A as well as its LPS stimulated the splenocytes from C3H/HeN and C3H/HeJ mice.