The chronic administration of phenobarbital (180 mg/day p.o.) alters the binding, bioavailability, metabolism and pharmacokinetics of propranolol. Consequently, phenobarbital affects the pharmacological activity of propranolol as measured by inhibition of isoproterenol tachycardia in dogs. Altered binding affects beta blockade in two ways; a reduction in the free fraction and the volume of distribution. To separate the effects of active metabolites from the parent drug, we have used an integrated form of the equation (DR -- 1) = K.(p), where DR is the dose ratio and p is the concentration of the free (unbound) propranolol in plasma. The activity due to propranolol itself is subtracted from the total observed amount of beta blockade. In this way, phenobarbital was shown to increase the amount of beta blockade which was due to active metabolites. Phenobarbital treatment shortened the time course of beta blockade. The beta blocking half-life for propranolol followed its pharmacokinetic half-life closely for a variety of experimental conditions. This suggests that pharmacological activity data could be used to describe pharmacokinetics without measuring blood concentrations.