Five patients, 4 boys and 1 girl aged 13-41 months, developed invasive Haemophilus influenzae type b (Hib) disease (2 epiglottitis, 3 meningitis) despite full (or at least 3 times) vaccination. At admission as well during convalescence, 3 out of 5 had IgG anti Hib antibody levels < or = 5 U/ml. Serum immunoglobulin levels, including IgG subclasses, as well as complement were normal in all cases. In 2 of the 3, booster vaccinations with Hib conjugate vaccine elicited adequate antibody titres. Since the incorporation of the conjugated Hib polysaccharide tetanus toxoid vaccine (HibTT) in the National Vaccination Programme in the Netherlands, the number of invasive infections caused by Hib has dropped significantly. Causes of Hib conjugate vaccine failures are mostly unknown. In about one-third of the cases serum immunoglobulin levels are deficient, most often IgG2 or IgM. Susceptibility to Hib infection is in part also genetically determined. In the follow-up of Hib vaccine failures, anti Hib antibody titres should be determined. Booster vaccinations may be necessary.