The aim of the present investigation was to determine whether tetracycline accelerated the hepatic toxicity of portacaval anastomosis and whether this could be reflected by changes in pharmacokinetics of the drug. Side-to-side portacaval shunts were constructed and converted to end-to-side by ligating the hepatic side of the portal vein in dogs. The results of this study showed that the i.v. infusion of tetracycline (50 mg/kg) to shunted animals caused rapid deterioration in hepatic and renal functions followed by the eventual transition of these animals from stage I to stage II liver disease. This was reflected by a 3- to 6-fold increase in the serum level of bilirubin, alkaline phosphatase, serum glutamic-oxalacetic transaminase, blood urea nitrogen and creatinine as compared with the levels of those produced in serum of dogs before and after the construction of the shunt before the administration of tetracycline. Kinetic analysis revealed a significant prolongation in the elimination half-life (38.2 +/- 4.2 hr) of the shunted dogs as compared with controls (14.5 +/- 1.5 hr) after the i.v. administration of tetracycline. This was accompanied by an appreciable reduction of elimination rate constant. In contrast to shunted animals, control animals exhibited no behavioral side effects after the administration of tetracycline.