High concentrations of levofloxacin in soft tissues and body fluids, including gallbladder and bile, have been repeatedly reported, but no study on its penetration into human liver tissue after single-shot application has yet been published. Levofloxacin 500 mg was administered intravenously to 28 patients scheduled for liver resection. Blood samples were taken after the end of infusion and at the time of liver resection; concomitantly, a tissue specimen was also obtained. Serum concentrations (mean+/-standard deviation) 10 min after the end of infusion were 6.59+/-1.72 microg/mL and decreased only slightly throughout the operation. At the time of liver resection, levofloxacin concentrations in liver tissue were 18.14+/-5.44 microg/g with corresponding serum concentrations of 4.84+/-1.37 microg/mL. The tissue/serum ratio (3.72+/-0.73 at the time of resection) was nearly constant over the sampling period ranging from 0.4 h to 3.8 h after the end of infusion, indicating a fast distribution of levofloxacin into the liver tissue. The tissue concentrations showed a significant correlation with serum concentrations and an inverse correlation with the grade of steatosis but not cirrhosis. Infectious post-operative complications were not observed. Levofloxacin penetrates into liver tissue exceptionally well and fast and is therefore a good candidate for antibiotic prophylaxis before invasive hepatobiliary procedures such as liver surgery as well as for treatment of biliary tract infections caused by levofloxacin-susceptible microorganisms.