Haemophilus influenzae type b (Hib) grown in broth is much more sensitive to killing by antibody to lipopolysaccharide (LPS) and complement than is Hib in bacteremic rats; upon brief incubation with low-molecular-weight components of plasma or serum, however, broth-grown cells are phenotypically converted to a resistance resembling that in vivo. This conversion was found to consume a limiting factor in serum filtrate, to require protein synthesis, and to occur independently of the presence of capsule. Less antibody to LPS bound to cells of the resistant (Res) phenotype than to cells of the sensitive (Sen) phenotype. In electrophoretic analysis the mobility of LPS bands was identical, but the staining density of the LPS bands extracted from Res cells (with phenol-water) was two-to fourfold greater than from an equal number of Sen cells. A similar differential was found in an immunologic assay of LPS in the extracts. Thus, Hib in the Res phenotype (and perhaps Hib in vivo) contains more LPS than Hib in the Sen phenotype, but its LPS appears less accessible to antibody.