In a 3-year nationwide prospective study on pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel, 1258 invasive infections with a known focus were observed. Meningitis was found in 482 (38%): 56%, 16%, and 76% of all infections by H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. The incidence of meningitis during the first year of life was 67.1, 17.5, and 9.5/100,000 for H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively, and in children < 5 years old it was 18.5, 5.3, and 5.2. Extrapolated for a population in which 100,000 live births occur yearly, 2097 hospital days were required. The case fatality rate was 2.2%, 5.9%, and 6.3% for H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. Boys were affected significantly more often than girls, but mortality was higher among girls. On the basis of the observed serotypes and age distribution, even with optimal vaccine development in the next 5 years, it is not likely that > 50% of all cases will be prevented.