A study was carried out using an experimental biliary infection model to investigate the pharmacokinetic characteristics and therapeutic effect of cefbuperazone in the rabbit. Thirty rabbits were divided into three equal groups; a control group of normal animals, a group of infected animals receiving no cefbuperazone, and a group of infected animals receiving 50 mg cefbuperazone/kg intramuscularly. The experimental infection was made by direct inoculation of a suspension of E. coli into the common bile duct after ligation. The results showed that extremely high levels of cefbuperazone were achieved in bile and tissues of the biliary tract and were higher than those in the blood. Moreover, the levels were maintained at effective concentrations even after 6 hours. Viable bacterial cells from bile and the gall-bladder were barely detectable 24 and 48 hours after infection in the cefbuperazone-treated group, whilst counts remained high in the other infected group. White blood cell counts were increased at 24 hours after infection but were significantly lower in the cefbuperazone-treated group. Histological examination revealed marked inflammatory changes in the gall-bladder and bile duct of infected, untreated animals but few, mild changes only were seen in cefbuperazone-treated animals. Similarly, total bilirubin and liver enzymes were markedly increased in infected animals, but transaminases and alkaline phosphatase were significantly lower in the treated compared to the untreated group. The findings indicate, therefore, that cefbuperazone can be a useful antibiotic in biliary infection.