Interval cerebrospinal fluid (CSF) analysis is often performed to assess efficacy of treatment for bacterial meningitis. The authors reviewed 101 cases of pediatric bacterial meningitis resulting from Hemophilus influenzae type b in which analysis of CSF occurred on admission and between 48 and 72 hours after initiation of parenteral antibiotic therapy; of these, only one patient had a positive repeat CSF culture. Of the 100 cases with sterile CSF on repeat culture, there was no instance of recrudescence of infection during hospitalization. The following characterized the interval changes in CSF profile of this group: 100 (100%) with persistence of pleocytosis; 14 (14%) with differential cell count conversion from polymorphonuclear neutrophil leukocyte (PMN) predominance to relative lymphocytosis; 96 of 98 (98%) with initial positive Gram-stained smear with negative results for organisms; 53 of 75 (71%) with normalization of initial hypoglycorrhachia; and 10 of 94 (11%) with normalization of initial abnormally elevated protein levels. The differences in mean values of CSF total white blood cell counts, percentage PMNs, and glucose and protein concentrations on presentation and between 48-72 hours of therapy were highly significant (P less than 0.0001). After 48 hours of effective antibiotic therapy for H. influenzae type b meningitis, CSF pleocytosis and abnormally elevated protein concentration are usually preserved, whereas hypoglycorrhachia usually resolves; it is not uncommon for the differential cell count to convert from a PMN predominance to a relative lymphocytosis. Significant alteration in all CSF parameters associated with H. influenzae type b meningitis can occur after 48 hours of effective parenteral antibiotic therapy.