A new principle for estimating hepatic blood flow rates is demonstrated in steady-state experiments in rats in which p-aminohippurate, labeled with either 14C or 3H, was infused into the portal vein, with simultaneous infusion into the tail vein of the same compound labeled with the other isotope. Hepatic blood flow and hepatic extraction ratios were calculated from measurements of urinary and biliary excretion rates and blood concentrations of each isotope. The principle may be used to calculate hepatic blood flow from measurements of urinary excretion and systemic blood concentrations of drug and metabolite after intravenous injections of radiolabeled drug and precursor.