The beta-blocking effect of 4 beta-adrenoceptor antagonists with different pharmacokinetic properties was studied after intravenous and intraportal administration to control rats and to rats with experimental inflammation. In rats with inflammation the effects of propranolol and oxprenolol, which are mainly bound to alpha 1-acid glycoprotein (alpha 1-AGP), were significantly less after intravenous administration, but not after intraportal administration. In contrast, for metoprolol and atenolol, which are only negligibly serum bound, no difference was observed between control rats and rats with inflammation for either route of administration. Total and unbound serum concentrations of propranolol were measured 20 min after intravenous and intraportal administration. After intravenous administration, in the rats with inflammation total concentrations of propranolol were more than twice, and unbound concentrations less than half those of control rats. After intraportal administration the total concentrations were 8 times, and the unbound concentrations 3 times higher in the rats with inflammation. There was a significant correlation between the beta-blocking effect and the unbound concentrations of propranolol after intravenous administration, but not after intraportal administration. The latter finding is probably because the unbound concentrations were supramaximal.