To explore whether bile duct ligation increased the risk for gentamicin nephrotoxicity, male Wistar rats were subjected to bile duct ligation or sham surgery and given either gentamicin 20 mg/kg or saline twice daily intraperitoneally for 8 days. Bile duct ligated and gentamicin injected rats elicited a decline in renal function and tubular cell necrosis after 8 days of treatment whereas equal dosage regimen in sham operated rats exhibited no evidence of renal dysfunction. In addition, though serum and kidney gentamicin levels were higher in bile duct ligated rats (1.84 +/- 0.11 micrograms/ml versus 0.20 +/- 0.03 microgram/ml, and 1453 +/- 164 micrograms/g versus 698 +/- 138 micrograms/g of cortex, respectively, P less than 0.05). The data indicate that complete biliary obstruction enhances renal sensitivity to gentamicin.