Some areas of the world are known to have a low incidence of Haemophilus influenzae type b meningitis, although the reasons for this are unknown. Furthermore, no complete evaluation of the worldwide variation in the incidence of Haemophilus influenzae type b meningitis has been published. In the current study, the published medical literature was reviewed to identify all studies conducted in the absence of routine childhood Haemophilus influenzae type b conjugate vaccination that reported an incidence of Haemophilus influenzae type b meningitis among children less than 5 years of age. To test the hypothesis that antibiotic use may have influenced the incidence of meningitis, incidence rates were correlated with antibiotic resistance. Seventy-one articles reported an incidence of childhood Haemophilus influenzae type b meningitis (median, 21 cases per 100,000 population per year; range, 1-95 cases per 100,000 population per year), with Asia and central/southern Europe reporting lower incidences than other areas (median, 5 and 11 cases per 100,000 per year, respectively). Within these regions of low incidence, the proportion of cerebrospinal fluid specimens that had a leukocyte count or glucose or protein level suggestive of bacterial meningitis but from which no organism was identified was low, indicating that there was no large reservoir of Haemophilus influenzae type b meningitis that went undetected by the laboratory. Study-specific incidence rates of meningitis correlated with the proportion of isolates resistant to ampicillin (or producing beta-lactamase) (R2=0.35. P=0.0014). The incidence of Haemophilus influenzae type b meningitis is substantially lower in some areas of the world than others, but this difference is unlikely to be related primarily to laboratory methodology. In contrast, antibiotic use may contribute to the observed differences in incidence.