Porphyromonas gingivalis 381 lipid A induced strong mitogenic response in splenic B cells separated from LPS-non-responsive C3H/HeJ mice as well as LPS-responsive C3H/HeN mice, by using a magnetic cell sorting system. The lipid A also exhibited mitogenic activity in splenic T cells. P. gingivalis lipid A induced lower production of interleukin-1 beta (IL-1 beta) in splenic macrophage cultures and exhibited a comparable IL-6 producing activity in splenic B cells of C3H/HeN mice as compared to Escherichia coli-type synthetic lipid A (compound 506) and monophosphoryl lipid A from Salmonella minnesota Re 595 (MLA). Furthermore, P. gingivalis lipid A, but not compound 506 nor MLA, induced low IL-1 beta and high IL-6 production in C3H/HeJ mice. C3H/HeJ T cells in response to P. gingivalis lipid A stimulation resulted in definite IL-2 mRNA and its production, whereas IL-4 response was scarcely active in both C3H/HeN and C3H/HeJ T cells. P. gingivalis lipid A increased tyrosine, serine/threonine phosphorylation of proteins with various major induced bands in splenic B cells of both C3H/HeN and C3H/HeJ mice. Thus, P. gingivalis lipid A stimulated the splenic immunocytes of C3H/HeJ as well as C3H/HeN mice.