The mitogenicity and lethal toxicity of chemically synthesized lipid A analogs, in which 2,3-acyloxyacylglucosamine-4-phosphate linked to tetraacetyl-N-acetylneuraminic acid (compound A-207) or to N-acetylneuraminic acid (compound A-307), were examined. Although the mitogenic activity of the synthetic compounds was weaker than that of bacterial LPS, doses of 10-50 μg/ml of A-207 and 5-10 μg/ml of A-307 were capable of increasing incorporation of [ 3 H]thymidine into cultured spleen cells of C57BL/6 mice. Lethal toxicity of A-207 was observed at 10 μg/mouse in C57BL/6 mice sensitized with D-galactosamine hydrochloride. However, the attachment of tetraacetyl-N-acetylneuraminic acid or N-acetylneuraminic acid does not appear to enhance the biological activity of acyloxyacylglucosamine-4-phosphate.