It has been suggested that serotype influences severity of experimental pneumococcal meningitis. This hypothesis was tested with strains of serotypes 1, 5, 6B, 7F, 14, and 23F, prevalent in Israel, in an experimental rabbit model. Cerebrospinal fluid (CSF) bacterial titers, leukocyte densities, concentrations of lactate, protein, and glucose, tumor necrosis factor-alpha levels, brain water content, and cerebral blood flow were measured 18 h after inoculation of pneumococci. Serotypes 5 and 7F exhibited mild inflammatory responses (leukocytosis <1000/mm3, lactate <4 mmol/L); types 6B, 14, and 23F showed severe inflammatory responses (leukocytosis >5000/mm3, lactate >10 mmol/L); serotype 1 had intermediate inflammatory responses but exceptionally high CSF bacterial titers. Leukocyte count correlated with all other variables; lactate with all except brain water content. On the basis of 6 Streptococcus pneumoniae serotypes, three discrete levels of inflammatory responses could be delineated in experimental pneumococcal meningitis.