In an attempt to examine whether routes of bacterial entry into the central nervous system have any bearing on subsequent changes in blood–brain barrier permeability, we examined cerebrospinal fluid (CSF) penetration of circulating¹²⁵I-albumin in two different models of experimental meningitis due to K1Escherichia coli,type III group B streptococcus, orHaemophilus influenzaetype b in infant rats: hematogenous meningitis subsequent to subcutaneous inoculation of bacteria vs meningitis induced by direct inoculation of bacteria into the CSF via the cisterna magna. In the model of hematogenous meningitis, the mean CSF penetration was significantly greater in animals withH. influenzaetype b meningitis than in those with meningitis due to K1E. colior type III group B streptococcus. In contrast, the mean CSF penetration was significantly enhanced in all animals with meningitis induced by intracisternal inoculation regardless of infecting pathogens. Tumor necrosis factor activity in CSF appeared to correlate with the functional penetration of circulating albumin across the blood–brain barrier in both models of experimental meningitis. These findings suggest that the alterations of blood–brain barrier permeability during development of experimental meningitis may vary for different models of inducing meningitis and that the mechanisms responsible for these different permeability changes may be multifactorial.