Impaired mental status is a poorly understood manifestation of sepsis and may be associated with altered permeability of the blood-brain barrier. To examine the possibility that sepsis affects permeability of the blood-brain barrier, rats were infected with a peritoneal implant consisting of sterilized feces, barium sulfate, and 10(8) colony forming units (CFU) of Escherichia coli. Using this model, reproducible episodes of peritonitis with bacteremia resulted. Rats were sacrificed hourly after 5 min circulation of 100 mg horseradish peroxidase. Animals were perfused-fixed and the brains removed. Representative coronal sections were stained for peroxidase reaction product and cerebral blood vessels were examined microscopically for evidence of HRP staining and extravasation. The number of stained cerebral vessels from infected rats was increased at all times compared to uninfected control rats. Extravasation of horseradish peroxide within neuropil was significantly higher in hours 1, 4 and 5 as compared to controls. The lack of significant increase in hours 2 and 3 may suggest transient closing or repair of the tight junctions. We conclude that peritonitis and bacteremia are associated with increased permeability of the blood-brain barrier.