To better define the mechanism of the increased plasma concentration of propranolol (PL) after meals, the effect of the dietary constitution of a meal on the kinetics of PL and beta-naphthoxylactic acid (NLA), a main metabolite, after administration of the drug, was investigated in rats. Additionally, the hepatic uptake of PL and cytochrome P-450 (P-450) content and uridine 5'-diphosphoglucuronyltransferase (UDPGT) activity in liver were measured after glucose intake. As a result, protein (skim milk) intake slightly, but not significantly, increased the area under the plasma concentration-time curve (AUC) and bioavailability of PL, with a slight increase (16%) in hepatic blood flow, and enhanced PL metabolism to NLA. Soybean oil and fatty acid intake significantly decreased the bioavailability of PL, while glucose intake dramatically decreased the hepatic uptake of PL and P-450 content at high glucose levels, resulting in a decrease in the plasma PL concentration at the initial time period and in the inhibition of a metabolic conversion to NLA. Thus, a possible mechanism involved in the effect of food on PL bioavailability could have been due largely to the decreased microsomal P-450 content and hepatic uptake of PL after glucose intake, but only partly to the increased hepatic blood flow after protein intake.