The capsular polysaccharide of Haemophilus influenzae serotype b [(3)-beta-D-ribose-(1-1)-ribitol-5-phosphate] is a major virulence factor and a target for serum antibodies which protect individuals against invasive infections. Studies in an experimental rat model of meningitis, using genetically defined H. influenzae transformants, provide evidence that chromosomal genes within or limited to a region (cap b) containing genes necessary for type b capsule are critical for efficient intravascular survival of H. influenzae. Within cap b there is a duplication of a 17 kb region organized as direct repeats separated by a smaller (1-2 kb) region of non-repeated DNA. Homologous recombination between the direct repeats is rec dependent and results in high-frequency loss of capsule expression and virulence.