The influence of i.v. administration of 10 mg/kg recombinant human interleukin-1β (rhIL-1/sgb), a putative mediator of inflammation, on the pharmacokinetics and metabolism of the propranolol enantiomers was studied in rats aged 3, 12 and 24 months. After oral administration of rac-propranolol to control rats of the three age groups, the plasma concentrations of ( R-propranolol) were higher than those of ( S)-propranolol. Administration of IL-1β increased the plasma concentrations of the ( R)-enantiomer markedly and significantly, those of the ( S)-enantiomer only to a lesser degree. For both enantiomers an important increase in plasma binding was found in the IL-1β-treated rats, which was linked to the increase in α 1-acid glycoprotein levels. The in vitro clearance, measured in 3-month-old rats using the 9000 g liver fraction, was for neither of the propranolol enantiomers influenced by IL-1β treatment, which is in keeping with the unchanged cytochrome P450 content. The enantioselective influence of IL-1β treatment on the pharmacokinetics of propranolol was also present in 12- and 24-month-old rats, although somewhat less pronounced in the latter group. Our results show an enantioselective influence of IL-1β treatment on the pharmacokinetics of propranolol in the rat, favouring the ( R enantiomer.