We show that formaldehyde fixation of Salmonella typhimurium lipopolysaccharide (LPS) to ribosomes purified from Brucella abortus induced a primary immunoglobulin M (IgM) response to LPS in C3H/HeJ mice and upon revaccination resulted in elevated titers of IgM and induction of IgG antibody to the O antigens of LPS, as measured by an enzyme-linked immunosorbent assay. A similar LPS-Aspergillus fumigatus ribosomal complex yielded IgM and IgG antibody to LPS only after secondary stimulation. These results demonstrate that the hyporesponsiveness of C3H/HeJ mice with respect to antibody formation to LPS can be overcome by complexing this molecule to ribosomal particles and provide a theoretical mechanism for the action of some "ribosomal" vaccines. The results are compatible with the hypothesis that LPS in complex with the ribosomes is converted to a T-dependent form of the antigen to which the C3H/HeJ mice can respond.